Iterative non-sequential protein structural alignment.

PubMed

Salem, Saeed; Zaki, Mohammed J; Bystroff, Christopher

2009-06-01

Structural similarity between proteins gives us insights into their evolutionary relationships when there is low sequence similarity. In this paper, we present a novel approach called SNAP for non-sequential pair-wise structural alignment. Starting from an initial alignment, our approach iterates over a two-step process consisting of a superposition step and an alignment step, until convergence. We propose a novel greedy algorithm to construct both sequential and non-sequential alignments. The quality of SNAP alignments were assessed by comparing against the manually curated reference alignments in the challenging SISY and RIPC datasets. Moreover, when applied to a dataset of 4410 protein pairs selected from the CATH database, SNAP produced longer alignments with lower rmsd than several state-of-the-art alignment methods. Classification of folds using SNAP alignments was both highly sensitive and highly selective. The SNAP software along with the datasets are available online at http://www.cs.rpi.edu/~zaki/software/SNAP.

Axial superresolution via multiangle TIRF microscopy with sequential imaging and photobleaching

PubMed Central

Fu, Yan; Winter, Peter W.; Rojas, Raul; Wang, Victor; McAuliffe, Matthew; Patterson, George H.

2016-01-01

We report superresolution optical sectioning using a multiangle total internal reflection fluorescence (TIRF) microscope. TIRF images were constructed from several layers within a normal TIRF excitation zone by sequentially imaging and photobleaching the fluorescent molecules. The depth of the evanescent wave at different layers was altered by tuning the excitation light incident angle. The angle was tuned from the highest (the smallest TIRF depth) toward the critical angle (the largest TIRF depth) to preferentially photobleach fluorescence from the lower layers and allow straightforward observation of deeper structures without masking by the brighter signals closer to the coverglass. Reconstruction of the TIRF images enabled 3D imaging of biological samples with 20-nm axial resolution. Two-color imaging of epidermal growth factor (EGF) ligand and clathrin revealed the dynamics of EGF-activated clathrin-mediated endocytosis during internalization. Furthermore, Bayesian analysis of images collected during the photobleaching step of each plane enabled lateral superresolution (<100 nm) within each of the sections. PMID:27044072

A Developmental Perspective on Peer Rejection, Deviant Peer Affiliation, and Conduct Problems Among Youth.

PubMed

Chen, Diane; Drabick, Deborah A G; Burgers, Darcy E

2015-12-01

Peer rejection and deviant peer affiliation are linked consistently to the development and maintenance of conduct problems. Two proposed models may account for longitudinal relations among these peer processes and conduct problems: the (a) sequential mediation model, in which peer rejection in childhood and deviant peer affiliation in adolescence mediate the link between early externalizing behaviors and more serious adolescent conduct problems; and (b) parallel process model, in which peer rejection and deviant peer affiliation are considered independent processes that operate simultaneously to increment risk for conduct problems. In this review, we evaluate theoretical models and evidence for associations among conduct problems and (a) peer rejection and (b) deviant peer affiliation. We then consider support for the sequential mediation and parallel process models. Next, we propose an integrated model incorporating both the sequential mediation and parallel process models. Future research directions and implications for prevention and intervention efforts are discussed.

A Developmental Perspective on Peer Rejection, Deviant Peer Affiliation, and Conduct Problems among Youth

PubMed Central

Chen, Diane; Drabick, Deborah A. G.; Burgers, Darcy E.

2015-01-01

Peer rejection and deviant peer affiliation are linked consistently to the development and maintenance of conduct problems. Two proposed models may account for longitudinal relations among these peer processes and conduct problems: the (a) sequential mediation model, in which peer rejection in childhood and deviant peer affiliation in adolescence mediate the link between early externalizing behaviors and more serious adolescent conduct problems; and (b) parallel process model, in which peer rejection and deviant peer affiliation are considered independent processes that operate simultaneously to increment risk for conduct problems. In this review, we evaluate theoretical models and evidence for associations among conduct problems and (a) peer rejection and (b) deviant peer affiliation. We then consider support for the sequential mediation and parallel process models. Next, we propose an integrated model incorporating both the sequential mediation and parallel process models. Future research directions and implications for prevention and intervention efforts are discussed. PMID:25410430

Concise Syntheses of bis-Strychnos Alkaloids (-)-Sungucine, (-)-Isosungucine, and (-)-Strychnogucine B from (-)-Strychnine.

PubMed

Zhao, Senzhi; Teijaro, Christiana N; Chen, Heng; Sirasani, Gopal; Vaddypally, Shivaiah; Zdilla, Michael J; Dobereiner, Graham E; Andrade, Rodrigo B

2016-08-08

The first chemical syntheses of complex, bis-Strychnos alkaloids (-)-sungucine (1), (-)-isosungucine (2), and (-)-strychnogucine B (3) from (-)-strychnine (4) is reported. Key steps included (1) the Polonovski-Potier activation of strychnine N-oxide; (2) a biomimetic Mannich coupling to forge the signature C23-C5' bond that joins two monoterpene indole monomers; and (3) a sequential HBr/NaBH3 CN-mediated reduction to fashion the ethylidene moieties in 1-3. DFT calculations were employed to rationalize the regiochemical course of reactions involving strychnine congeners. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Technology: Digital Photography in an Inner-City Fifth Grade, Part 1

ERIC Educational Resources Information Center

Riner, Phil

2005-01-01

Research tells us we can learn complex tasks most easily if they are taught in "small sequential steps." This column is about the small sequential steps that unlocked the powers of digital photography, of portraiture, and of student creativity. The strategies and ideas described in this article came as a result of working with…

Proposed hardware architectures of particle filter for object tracking

NASA Astrophysics Data System (ADS)

Abd El-Halym, Howida A.; Mahmoud, Imbaby Ismail; Habib, SED

2012-12-01

In this article, efficient hardware architectures for particle filter (PF) are presented. We propose three different architectures for Sequential Importance Resampling Filter (SIRF) implementation. The first architecture is a two-step sequential PF machine, where particle sampling, weight, and output calculations are carried out in parallel during the first step followed by sequential resampling in the second step. For the weight computation step, a piecewise linear function is used instead of the classical exponential function. This decreases the complexity of the architecture without degrading the results. The second architecture speeds up the resampling step via a parallel, rather than a serial, architecture. This second architecture targets a balance between hardware resources and the speed of operation. The third architecture implements the SIRF as a distributed PF composed of several processing elements and central unit. All the proposed architectures are captured using VHDL synthesized using Xilinx environment, and verified using the ModelSim simulator. Synthesis results confirmed the resource reduction and speed up advantages of our architectures.

Structural profiling of individual glycosphingolipids in a single thin-layer chromatogram by multiple sequential immunodetection matched with Direct IR-MALDI-o-TOF mass spectrometry.

PubMed

Souady, Jamal; Soltwisch, Jens; Dreisewerd, Klaus; Haier, Jörg; Peter-Katalinić, Jasna; Müthing, Johannes

2009-11-15

The thin-layer chromatography (TLC) immunoenzyme overlay assay is a widely used tool for antibody-mediated identification of glycosphingolipids (GSLs) in mixtures. However, because the majority of GSLs is left unexamined in a chromatogram of a single assay, we developed a novel method that permits detection of various GSLs by sequential multiple immunostaining combined with individual coloring of GSLs in the same chromatogram. Specific staining was achieved by means of primary anti-GSL antibodies, directed against lactosylceramide, globotriaosylceramide, and globotetraosylceramide, in conjunction with alkaline phosphatase (AP)- or horseradish peroxidase (HRP)-conjugated secondary antibodies together with the appropriate chromogenic substrates. Triple coloring with 5-bromo-4-chloro-3-indolyl phosphate (BCIP)-AP, Fast Red-AP, and 3,3'-diaminobenzidine (DAB)-HRP resulted in blue, red, and black precipitates, respectively, following three sequential immunostaining rounds. Structures of antibody-detected GSLs were determined by direct coupling of TLC with infrared matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry. This combinatorial technique was used to demonstrate structural GSL profiling of crude lipid extracts from human hepatocellular cancer. This powerful technology allows efficient structural characterization of GSLs in small tissue samples and marks a further step forward in the emerging field of glycosphingolipidomics.

A versatile semi-permanent sequential bilayer/diblock polymer coating for capillary isoelectric focusing.

PubMed

Bahnasy, Mahmoud F; Lucy, Charles A

2012-12-07

A sequential surfactant bilayer/diblock copolymer coating was previously developed for the separation of proteins. The coating is formed by flushing the capillary with the cationic surfactant dioctadecyldimethylammonium bromide (DODAB) followed by the neutral polymer poly-oxyethylene (POE) stearate. Herein we show the method development and optimization for capillary isoelectric focusing (cIEF) separations based on the developed sequential coating. Electroosmotic flow can be tuned by varying the POE chain length which allows optimization of resolution and analysis time. DODAB/POE 40 stearate can be used to perform single-step cIEF, while both DODAB/POE 40 and DODAB/POE 100 stearate allow performing two-step cIEF methodologies. A set of peptide markers is used to assess the coating performance. The sequential coating has been applied successfully to cIEF separations using different capillary lengths and inner diameters. A linear pH gradient is established only in two-step CIEF methodology using 3-10 pH 2.5% (v/v) carrier ampholyte. Hemoglobin A(0) and S variants are successfully resolved on DODAB/POE 40 stearate sequentially coated capillaries. Copyright © 2012 Elsevier B.V. All rights reserved.

Behavioral preference in sequential decision-making and its association with anxiety.

PubMed

Zhang, Dandan; Gu, Ruolei

2018-06-01

In daily life, people often make consecutive decisions before the ultimate goal is reached (i.e., sequential decision-making). However, this kind of decision-making has been largely overlooked in the literature. The current study investigated whether behavioral preference would change during sequential decisions, and the neural processes underlying the potential changes. For this purpose, we revised the classic balloon analogue risk task and recorded the electroencephalograph (EEG) signals associated with each step of decision-making. Independent component analysis performed on EEG data revealed that four EEG components elicited by periodic feedback in the current step predicted participants' decisions (gamble vs. no gamble) in the next step. In order of time sequence, these components were: bilateral occipital alpha rhythm, bilateral frontal theta rhythm, middle frontal theta rhythm, and bilateral sensorimotor mu rhythm. According to the information flows between these EEG oscillations, we proposed a brain model that describes the temporal dynamics of sequential decision-making. Finally, we found that the tendency to gamble (as well as the power intensity of bilateral frontal theta rhythms) was sensitive to the individual level of trait anxiety in certain steps, which may help understand the role of emotion in decision-making. © 2018 Wiley Periodicals, Inc.

Room-temperature current blockade in atomically defined single-cluster junctions

NASA Astrophysics Data System (ADS)

Lovat, Giacomo; Choi, Bonnie; Paley, Daniel W.; Steigerwald, Michael L.; Venkataraman, Latha; Roy, Xavier

2017-11-01

Fabricating nanoscopic devices capable of manipulating and processing single units of charge is an essential step towards creating functional devices where quantum effects dominate transport characteristics. The archetypal single-electron transistor comprises a small conducting or semiconducting island separated from two metallic reservoirs by insulating barriers. By enabling the transfer of a well-defined number of charge carriers between the island and the reservoirs, such a device may enable discrete single-electron operations. Here, we describe a single-molecule junction comprising a redox-active, atomically precise cobalt chalcogenide cluster wired between two nanoscopic electrodes. We observe current blockade at room temperature in thousands of single-cluster junctions. Below a threshold voltage, charge transfer across the junction is suppressed. The device is turned on when the temporary occupation of the core states by a transiting carrier is energetically enabled, resulting in a sequential tunnelling process and an increase in current by a factor of ∼600. We perform in situ and ex situ cyclic voltammetry as well as density functional theory calculations to unveil a two-step process mediated by an orbital localized on the core of the cluster in which charge carriers reside before tunnelling to the collector reservoir. As the bias window of the junction is opened wide enough to include one of the cluster frontier orbitals, the current blockade is lifted and charge carriers can tunnel sequentially across the junction.

Evaluation of sequential extraction procedures for soluble and insoluble hexavalent chromium compounds in workplace air samples.

PubMed

Ashley, Kevin; Applegate, Gregory T; Marcy, A Dale; Drake, Pamela L; Pierce, Paul A; Carabin, Nathalie; Demange, Martine

2009-02-01

Because toxicities may differ for Cr(VI) compounds of varying solubility, some countries and organizations have promulgated different occupational exposure limits (OELs) for soluble and insoluble hexavalent chromium (Cr(VI)) compounds, and analytical methods are needed to determine these species in workplace air samples. To address this need, international standard methods ASTM D6832 and ISO 16740 have been published that describe sequential extraction techniques for soluble and insoluble Cr(VI) in samples collected from occupational settings. However, no published performance data were previously available for these Cr(VI) sequential extraction procedures. In this work, the sequential extraction methods outlined in the relevant international standards were investigated. The procedures tested involved the use of either deionized water or an ammonium sulfate/ammonium hydroxide buffer solution to target soluble Cr(VI) species. This was followed by extraction in a sodium carbonate/sodium hydroxide buffer solution to dissolve insoluble Cr(VI) compounds. Three-step sequential extraction with (1) water, (2) sulfate buffer and (3) carbonate buffer was also investigated. Sequential extractions were carried out on spiked samples of soluble, sparingly soluble and insoluble Cr(VI) compounds, and analyses were then generally carried out by using the diphenylcarbazide method. Similar experiments were performed on paint pigment samples and on airborne particulate filter samples collected from stainless steel welding. Potential interferences from soluble and insoluble Cr(III) compounds, as well as from Fe(II), were investigated. Interferences from Cr(III) species were generally absent, while the presence of Fe(II) resulted in low Cr(VI) recoveries. Two-step sequential extraction of spiked samples with (first) either water or sulfate buffer, and then carbonate buffer, yielded quantitative recoveries of soluble Cr(VI) and insoluble Cr(VI), respectively. Three-step sequential extraction gave excessively high recoveries of soluble Cr(VI), low recoveries of sparingly soluble Cr(VI), and quantitative recoveries of insoluble Cr(VI). Experiments on paint pigment samples using two-step extraction with water and carbonate buffer yielded varying percentages of relative fractions of soluble and insoluble Cr(VI). Sequential extractions of stainless steel welding fume air filter samples demonstrated the predominance of soluble Cr(VI) compounds in such samples. The performance data obtained in this work support the Cr(VI) sequential extraction procedures described in the international standards.

Sequential mediating effects of provided and received social support on trait emotional intelligence and subjective happiness: A longitudinal examination in Hong Kong Chinese university students.

PubMed

Ye, Jiawen; Yeung, Dannii Y; Liu, Elaine S C; Rochelle, Tina L

2018-04-03

Past research has often focused on the effects of emotional intelligence and received social support on subjective well-being yet paid limited attention to the effects of provided social support. This study adopted a longitudinal design to examine the sequential mediating effects of provided and received social support on the relationship between trait emotional intelligence and subjective happiness. A total of 214 Hong Kong Chinese undergraduates were asked to complete two assessments with a 6-month interval in between. The results of the sequential mediation analysis indicated that the trait emotional intelligence measured in Time 1 indirectly influenced the level of subjective happiness in Time 2 through a sequential pathway of social support provided for others in Time 1 and social support received from others in Time 2. These findings highlight the importance of trait emotional intelligence and the reciprocal exchanges of social support in the subjective well-being of university students. © 2018 International Union of Psychological Science.

Environmentally friendly microwave-assisted sequential extraction method followed by ICP-OES and ion-chromatographic analysis for rapid determination of sulphur forms in coal samples.

PubMed

Mketo, Nomvano; Nomngongo, Philiswa N; Ngila, J Catherine

2018-05-15

A rapid three-step sequential extraction method was developed under microwave radiation followed by inductively coupled plasma-optical emission spectroscopic (ICP-OES) and ion-chromatographic (IC) analysis for the determination of sulphur forms in coal samples. The experimental conditions of the proposed microwave-assisted sequential extraction (MW-ASE) procedure were optimized by using multivariate mathematical tools. Pareto charts generated from 2 3 full factorial design showed that, extraction time has insignificant effect on the extraction of sulphur species, therefore, all the sequential extraction steps were performed for 5 min. The optimum values according to the central composite designs and counter plots of the response surface methodology were 200 °C (microwave temperature) and 0.1 g (coal amount) for all the investigated extracting reagents (H 2 O, HCl and HNO 3 ). When the optimum conditions of the proposed MW-ASE procedure were applied in coal CRMs, SARM 18 showed more organic sulphur (72%) and the other two coal CRMs (SARMs 19 and 20) were dominated by sulphide sulphur species (52-58%). The sum of the sulphur forms from the sequential extraction steps have shown consistent agreement (95-96%) with certified total sulphur values on the coal CRM certificates. This correlation, in addition to the good precision (1.7%) achieved by the proposed procedure, suggests that the sequential extraction method is reliable, accurate and reproducible. To safe-guard the destruction of pyritic and organic sulphur forms in extraction step 1, water was used instead of HCl. Additionally, the notorious acidic mixture (HCl/HNO 3 /HF) was replaced by greener reagent (H 2 O 2 ) in the last extraction step. Therefore, the proposed MW-ASE method can be applied in routine laboratories for the determination of sulphur forms in coal and coal related matrices. Copyright © 2018 Elsevier B.V. All rights reserved.

An integrated direct loop-mediated isothermal amplification microdevice incorporated with an immunochromatographic strip for bacteria detection in human whole blood and milk without a sample preparation step.

PubMed

Lee, Dohwan; Kim, Yong Tae; Lee, Jee Won; Kim, Do Hyun; Seo, Tae Seok

2016-05-15

We have developed an integrated direct loop-mediated isothermal amplification (Direct LAMP) microdevice incorporated with an immunochromatographic strip (ICS) to identify bacteria contaminated in real samples. The Direct LAMP is a novel isothermal DNA amplification technique which does not require thermal cycling steps as well as any sample preparation steps such as cell lysis and DNA extraction for amplifying specific target genes. In addition, the resultant amplicons were colorimetrically detected on the ICS, thereby enabling the entire genetic analysis process to be simplified. The two functional units (Direct LAMP and ICS) were integrated on a single device without use of the tedious and complicated microvalve and tubing systems. The utilization of a slidable plate allows us to manipulate the fluidic control in the microchannels manually and the sequential operation of the Direct LAMP and ICS detection could be performed by switching the slidable plate to each functional unit. Thus, the combination of the direct isothermal amplification without any sample preparation and thermal cycling steps, the ICS based amplicon detection by naked eyes, and the slidable plate to eliminate the microvalves in the integrated microdevice would be an ideal platform for point-of-care DNA diaganotics. On the integrated Direct LAMP-ICS microdevice, we could analyze Staphylococcus aureus (S. aureus) and Escherichia coli O157:H7 (E. coli O157:H7) contaminated in human whole blood or milk at a single-cell level within 1h. Copyright © 2015 Elsevier B.V. All rights reserved.

Group sequential designs for stepped-wedge cluster randomised trials

PubMed Central

Grayling, Michael J; Wason, James MS; Mander, Adrian P

2017-01-01

Background/Aims: The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Methods: Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. Results: We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial’s type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. Conclusion: The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial. PMID:28653550

Group sequential designs for stepped-wedge cluster randomised trials.

PubMed

Grayling, Michael J; Wason, James Ms; Mander, Adrian P

2017-10-01

The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial.

The utilization of modified BCR three-step sequential extraction procedure for the fractionation of Cd, Cr, Cu, Ni, Pb and Zn in soil reference materials of different origins.

PubMed

Zemberyová, Mária; Barteková, Jana; Hagarová, Ingrid

2006-12-15

A modified three-step sequential extraction procedure for the fractionation of heavy metals, proposed by the Commission of the European Communities Bureau of Reference (BCR) has been applied to the Slovak reference materials of soils (soil orthic luvisols, soil rendzina and soil eutric cambisol), which represent pedologically different types of soils in Slovakia. Analyses were carried out by flame or electrothermal atomic absorption spectrometry (FAAS or ETAAS). The fractions extracted were: exchangeable (extraction step 1), reducible-iron/manganese oxides (extraction step 2), oxidizable-organic matter and sulfides (extraction step 3). The sum of the element contents in the three fractions plus aqua-regia extractable content of the residue was compared to the aqua-regia extractable content of the elements in the origin soils. The accuracy obtained by comparing the determined contents of the elements with certified values, using BCR CRM 701, certified for the extractable contents (mass fractions) of Cd, Cr, Cu, Ni, Pb and Zn in sediment following a modified BCR-three step sequential extraction procedure, was found to be satisfactory.

The relationship between internalized stigma and quality of life among people with mental illness: are self-esteem and sense of coherence sequential mediators?

PubMed

Świtaj, Piotr; Grygiel, Paweł; Chrostek, Anna; Nowak, Izabela; Wciórka, Jacek; Anczewska, Marta

2017-09-01

To elucidate the mechanism through which internalized stigma reduces the quality of life (QoL) of people with mental illness by exploring the mediating roles of self-esteem and sense of coherence (SOC). A cross-sectional analysis of 229 patients diagnosed with schizophrenia or affective disorders was undertaken to test a sequential mediation model assuming that more severe internalized stigma is related to lower self-esteem, which is associated with weaker SOC, which in turn relates to worse QoL. The proposed model was supported by the data. A sequential indirect effect from internalized stigma to QoL via self-esteem and SOC turned out to be significant [beta = -0.06, SE = 0.02; 95% CI (-0.11, -0.03)]. Support was also found for simple mediation models with either self-esteem or SOC as single mediators between internalized stigma and QoL. Self-esteem and SOC are personal resources that should be considered as potential targets of interventions aiming to prevent the harmful consequences of internalized stigma for the QoL of people receiving psychiatric treatment.

MOLECULAR MECHANISM OF HUMAN NRF2 ACTIVATION AND DEGRADATION: ROLE OF SEQUENTIAL PHOSPHORYLATION BY PROTEIN KINASE CK2

PubMed Central

Pi, Jingbo; Bai, Yushi; Reece, Jeffrey M.; Williams, Jason; Liu, Dianxin; Freeman, Michael L.; Fahl, William E.; Shugar, David; Liu, Jie; Qu, Wei; Collins, Sheila; Waalkes, Michael P.

2007-01-01

Nrf2 is a key transcription factor in the cellular response to oxidative stress. In this study we first identify two phosphorylated forms of endogenous human Nrf2 after chemically-induced oxidative stress and provide evidence that protein kinase CK2-mediated sequential phosphorylation plays potential role in Nrf2 activation and degradation. Human Nrf2 has a predicted molecular mass of 66 kDa. However, immunoblots showed that two bands at 98 and 118 kDa, which are identified as phosphorylated forms, are increased in response to Nrf2 inducers. In addition, human Nrf2 was found to be a substrate for CK2 which mediated two steps of phosphorylation, resulting in two forms of Nrf2 migrating with differing Mr at 98 kDa (Nrf2–98) and 118 kDa (Nrf2–118). Our results support a role in which calmodulin binding regulates CK2 activity, in that cold (25 °C) in Ca2+-free media (cold/Ca2+-free) decreased both cellular calcium levels and CK2-calmodulin binding and induced Nrf2–118 formation, the latter of which was prevented by CK2 specific inhibitors. Gel-shift assays showed that the Nrf2–118 generated under cold/Ca2+-free conditions does not bind to the antioxidant response element, indicating that Nrf2–98 has transcriptional activity. In contrast, Nrf2–118 is more susceptible to degradation. These results provide evidence for phosphorylation by CK2 as a critical controlling factor in Nrf2-mediated cellular antioxidant response. PMID:17512459

Sequential addition reactions of two molecules of Grignard reagents to thioformamides.

PubMed

Murai, Toshiaki; Ui, Kazuki; Narengerile

2009-08-07

Sequential addition reactions of two molecules of Grignard reagents to thioformamides were found to yield tertiary amines in an efficient manner. The addition of two different Grignard reagents can be accomplished by using one equivalent of arylmagnesium reagent in the first step. In the second step, a variety of reagents such as alkyl, alkenyl, aryl, and alkynyl reagents were used to afford the corresponding amines in good to high yields.

Effects of a combined parent-student alcohol prevention program on intermediate factors and adolescents' drinking behavior: A sequential mediation model.

PubMed

Koning, Ina M; Maric, Marija; MacKinnon, David; Vollebergh, Wilma A M

2015-08-01

Previous work revealed that the combined parent-student alcohol prevention program (PAS) effectively postponed alcohol initiation through its hypothesized intermediate factors: increase in strict parental rule setting and adolescents' self-control (Koning, van den Eijnden, Verdurmen, Engels, & Vollebergh, 2011). This study examines whether the parental strictness precedes an increase in adolescents' self-control by testing a sequential mediation model. A cluster randomized trial including 3,245 Dutch early adolescents (M age = 12.68, SD = 0.50) and their parents randomized over 4 conditions: (1) parent intervention, (2) student intervention, (3) combined intervention, and (4) control group. Outcome measure was amount of weekly drinking measured at age 12 to 15; baseline assessment (T0) and 3 follow-up assessments (T1-T3). Main effects of the combined and parent intervention on weekly drinking at T3 were found. The effect of the combined intervention on weekly drinking (T3) was mediated via an increase in strict rule setting (T1) and adolescents' subsequent self-control (T2). In addition, the indirect effect of the combined intervention via rule setting (T1) was significant. No reciprocal sequential mediation (self-control at T1 prior to rules at T2) was found. The current study is 1 of the few studies reporting sequential mediation effects of youth intervention outcomes. It underscores the need of involving parents in youth alcohol prevention programs, and the need to target both parents and adolescents, so that change in parents' behavior enables change in their offspring. (c) 2015 APA, all rights reserved).

General methods for analysis of sequential "n-step" kinetic mechanisms: application to single turnover kinetics of helicase-catalyzed DNA unwinding.

PubMed

Lucius, Aaron L; Maluf, Nasib K; Fischer, Christopher J; Lohman, Timothy M

2003-10-01

Helicase-catalyzed DNA unwinding is often studied using "all or none" assays that detect only the final product of fully unwound DNA. Even using these assays, quantitative analysis of DNA unwinding time courses for DNA duplexes of different lengths, L, using "n-step" sequential mechanisms, can reveal information about the number of intermediates in the unwinding reaction and the "kinetic step size", m, defined as the average number of basepairs unwound between two successive rate limiting steps in the unwinding cycle. Simultaneous nonlinear least-squares analysis using "n-step" sequential mechanisms has previously been limited by an inability to float the number of "unwinding steps", n, and m, in the fitting algorithm. Here we discuss the behavior of single turnover DNA unwinding time courses and describe novel methods for nonlinear least-squares analysis that overcome these problems. Analytic expressions for the time courses, f(ss)(t), when obtainable, can be written using gamma and incomplete gamma functions. When analytic expressions are not obtainable, the numerical solution of the inverse Laplace transform can be used to obtain f(ss)(t). Both methods allow n and m to be continuous fitting parameters. These approaches are generally applicable to enzymes that translocate along a lattice or require repetition of a series of steps before product formation.

Extrusion of amyloid fibrils to the extracellular space in experimental mesangial AL-amyloidosis: transmission and scanning electron microscopy studies and correlation with renal biopsy observations.

PubMed

Teng, Jiamin; Turbat-Herrera, Elba A; Herrera, Guillermo A

2014-04-01

In vitro studies have provided much information regarding the process of glomerular AL-amyloidogenesis. Research efforts have been successful in deciphering how glomerulopathic light chains interact with mesangial cells. The sequential steps involved in the genesis of amyloid fibrils include interactions with surface caveolae in mesangial cells and internalization of the monoclonal light chains through a clathrin-mediated process followed by trafficking in the mesangial cells to the mature lysosomal compartment where fibrils are formed. This manuscript focuses on how mesangial cells, once amyloid has been formed, deliver the fibrils to the extracellular matrix. The delivery of amyloid fibrils to the outside of the cells is carried out by lysosomes, which abut the mesangial cell membranes and extrude their contents into the extracellular space. This final step responsible for the fibrils to be present predominantly in the extracellular space is well demonstrated with scanning electron microscopy.

Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup.

PubMed

Hardarson, Thorir; Bungum, Mona; Conaghan, Joe; Meintjes, Marius; Chantilis, Samuel J; Molnar, Laszlo; Gunnarsson, Kristina; Wikland, Matts

2015-12-01

To study whether a culture medium that allows undisturbed culture supports human embryo development to the blastocyst stage equivalently to a well-established sequential media. Randomized, double-blinded sibling trial. Independent in vitro fertilization (IVF) clinics. One hundred twenty-eight patients, with 1,356 zygotes randomized into two study arms. Embryos randomly allocated into two study arms to compare embryo development on a time-lapse system using a single-step medium or sequential media. Percentage of good-quality blastocysts on day 5. Percentage of day 5 good-quality blastocysts was 21.1% (standard deviation [SD] ± 21.6%) and 22.2% (SD ± 22.1%) in the single-step time-lapse medium (G-TL) and the sequential media (G-1/G-2) groups, respectively. The mean difference (-1.2; 95% CI, -6.0; 3.6) between the two media systems for the primary end point was less than the noninferiority margin of -8%. There was a statistically significantly lower number of good-quality embryos on day 3 in the G-TL group [50.7% (SD ± 30.6%) vs. 60.8% (SD ± 30.7%)]. Four out of the 11 measured morphokinetic parameters were statistically significantly different for the two media used. The mean levels of ammonium concentration in the media at the end of the culture period was statistically significantly lower in the G-TL group as compared with the G-2 group. We have shown that a single-step culture medium supports blastocyst development equivalently to established sequential media. The ammonium concentrations were lower in the single-step media, and the measured morphokinetic parameters were modified somewhat. NCT01939626. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Increasing the sensitivity of reverse phase protein arrays by antibody-mediated signal amplification

PubMed Central

2010-01-01

Background Reverse phase protein arrays (RPPA) emerged as a useful experimental platform to analyze biological samples in a high-throughput format. Different signal detection methods have been described to generate a quantitative readout on RPPA including the use of fluorescently labeled antibodies. Increasing the sensitivity of RPPA approaches is important since many signaling proteins or posttranslational modifications are present at a low level. Results A new antibody-mediated signal amplification (AMSA) strategy relying on sequential incubation steps with fluorescently-labeled secondary antibodies reactive against each other is introduced here. The signal quantification is performed in the near-infrared range. The RPPA-based analysis of 14 endogenous proteins in seven different cell lines demonstrated a strong correlation (r = 0.89) between AMSA and standard NIR detection. Probing serial dilutions of human cancer cell lines with different primary antibodies demonstrated that the new amplification approach improved the limit of detection especially for low abundant target proteins. Conclusions Antibody-mediated signal amplification is a convenient and cost-effective approach for the robust and specific quantification of low abundant proteins on RPPAs. Contrasting other amplification approaches it allows target protein detection over a large linear range. PMID:20569466

Trauma exposure and cigarette smoking: the impact of negative affect and affect-regulatory smoking motives.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Beckham, Jean C; Vujanovic, Anka A; Schmidt, Norman B

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association.

Trauma Exposure and Cigarette Smoking: The Impact of Negative Affect and Affect-Regulatory Smoking Motives

PubMed Central

Farris, Samantha G.; Zvolensky, Michael J.; Beckham, Jean C.; Vujanovic, Anka A.; Schmidt, Norman B.

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association. PMID:25299617

Exploring the sequential lineup advantage using WITNESS.

PubMed

Goodsell, Charles A; Gronlund, Scott D; Carlson, Curt A

2010-12-01

Advocates claim that the sequential lineup is an improvement over simultaneous lineup procedures, but no formal (quantitatively specified) explanation exists for why it is better. The computational model WITNESS (Clark, Appl Cogn Psychol 17:629-654, 2003) was used to develop theoretical explanations for the sequential lineup advantage. In its current form, WITNESS produced a sequential advantage only by pairing conservative sequential choosing with liberal simultaneous choosing. However, this combination failed to approximate four extant experiments that exhibited large sequential advantages. Two of these experiments became the focus of our efforts because the data were uncontaminated by likely suspect position effects. Decision-based and memory-based modifications to WITNESS approximated the data and produced a sequential advantage. The next step is to evaluate the proposed explanations and modify public policy recommendations accordingly.

Multi-Level Sequential Pattern Mining Based on Prime Encoding

NASA Astrophysics Data System (ADS)

Lianglei, Sun; Yun, Li; Jiang, Yin

Encoding is not only to express the hierarchical relationship, but also to facilitate the identification of the relationship between different levels, which will directly affect the efficiency of the algorithm in the area of mining the multi-level sequential pattern. In this paper, we prove that one step of division operation can decide the parent-child relationship between different levels by using prime encoding and present PMSM algorithm and CROSS-PMSM algorithm which are based on prime encoding for mining multi-level sequential pattern and cross-level sequential pattern respectively. Experimental results show that the algorithm can effectively extract multi-level and cross-level sequential pattern from the sequence database.

Childhood Maltreatment and PTSD: Spiritual Well-Being and Intimate Partner Violence as Mediators

PubMed Central

Zhang, Huaiyu; Pittman, Delishia M.; Lamis, Dorian A.; Fischer, Nicole L.; Schwenke, Tomina J.; Carr, Erika R.; Shah, Sanjay; Kaslow, Nadine J.

2016-01-01

Childhood maltreatment places individuals, including African American women who are undereducated and economically disadvantaged, at risk for developing posttraumatic stress disorder (PTSD) symptoms. Participants were 192 African American women with a history in the prior year of both a suicide attempt and intimate partner violence (IPV) exposure. They were recruited from a public hospital that provides medical and mental health treatment to mostly low-income patients. A simple mediator model was used to examine if (1) existential well-being (sense of purpose) and/or religious well-being (relationship with God) mediated the link between childhood maltreatment and adult PTSD symptoms. Sequential multiple mediator models determined if physical and nonphysical IPV enhanced our understanding of the mediational association among the aforementioned variables. Findings suggest that existential well-being mediated the association between childhood maltreatment and adult PTSD symptoms in a simple mediator model, and existential well-being and recent nonphysical IPV served as sequential multiple mediators of this link. However, religious well-being and physical IPV were not significant mediators. Findings underscore the importance of enhancing existential well-being in the treatment of suicidal African American women with a history of childhood maltreatment and IPV. PMID:26989343

Physical activity in England: who is meeting the recommended level of participation through sports and exercise?

PubMed

Anokye, Nana Kwame; Pokhrel, Subhash; Buxton, Martin; Fox-Rushby, Julia

2013-06-01

Little is known about the correlates of meeting recommended levels of participation in physical activity (PA) and how this understanding informs public health policies on behaviour change. To analyse who meets the recommended level of participation in PA in males and females separately by applying 'process' modelling frameworks (single vs. sequential 2-step process). Using the Health Survey for England 2006, (n = 14 142; ≥ 16 years), gender-specific regression models were estimated using bivariate probit with selectivity correction and single probit models. A 'sequential, 2-step process' modelled participation and meeting the recommended level separately, whereas the 'single process' considered both participation and level together. In females, meeting the recommended level was associated with degree holders [Marginal effect (ME) = 0.013] and age (ME = -0.001), whereas in males, age was a significant correlate (ME = -0.003 to -0.004). The order of importance of correlates was similar across genders, with ethnicity being the most important correlate in both males (ME = -0.060) and females (ME = -0.133). In females, the 'sequential, 2-step process' performed better (ρ = -0.364, P < 0.001) than that in males (ρ = 0.154). The degree to which people undertake the recommended level of PA through vigorous activity varies between males and females, and the process that best predicts such decisions, i.e. whether it is a sequential, 2-step process or a single-step choice, is also different for males and females. Understanding this should help to identify subgroups that are less likely to meet the recommended level of PA (and hence more likely to benefit from any PA promotion intervention).

Transportable Maps Software. Volume I.

DTIC Science & Technology

1982-07-01

being collected at the beginning or end of the routine. This allows the interaction to be followed sequentially through its steps by anyone reading the...flow is either simple sequential , simple conditional (the equivalent of ’if-then-else’), simple iteration (’DO-loop’), or the non-linear recursion...input raster images to be in the form of sequential binary files with a SEGMENTED record type. The advantage of this form is that large logical records

An Aid for Planning Programs in Career Education.

ERIC Educational Resources Information Center

Illinois State Board of Vocational Education and Rehabilitation, Springfield. Div. of Vocational and Technical Education.

Offered as an aid for developing sequential occupational education programs, the publication presents a concept in career education planning beginning with kindergarten and continuing through adult years. Career education goals are defined, and steps in planning sequential programs are outlined as follows: (1) organization of the occupational…

Expedited vocational assessment under the sequential evaluation process. Final rules.

PubMed

2012-07-25

We are revising our rules to give adjudicators the discretion to proceed to the fifth step of the sequential evaluation process for assessing disability when we have insufficient information about a claimant's past relevant work history to make the findings required for step 4. If an adjudicator finds at step 5 that a claimant may be unable to adjust to other work existing in the national economy, the adjudicator will return to the fourth step to develop the claimant's work history and make a finding about whether the claimant can perform his or her past relevant work. We expect that this new expedited process will not disadvantage any claimant or change the ultimate conclusion about whether a claimant is disabled, but it will promote administrative efficiency and help us make more timely disability determinations and decisions.

Development of a standardized sequential extraction protocol for simultaneous extraction of multiple actinide elements

DOE PAGES

Faye, Sherry A.; Richards, Jason M.; Gallardo, Athena M.; ...

2017-02-07

Sequential extraction is a useful technique for assessing the potential to leach actinides from soils; however, current literature lacks uniformity in experimental details, making direct comparison of results impossible. This work continued development toward a standardized five-step sequential extraction protocol by analyzing extraction behaviors of 232Th, 238U, 239,240Pu and 241Am from lake and ocean sediment reference materials. Results produced a standardized procedure after creating more defined reaction conditions to improve method repeatability. A NaOH fusion procedure is recommended following sequential leaching for the complete dissolution of insoluble species.

Sequential Aldol Condensation – Transition Metal-Catalyzed Addition Reactions of Aldehydes, Methyl Ketones and Arylboronic Acids

PubMed Central

Liao, Yuan-Xi; Xing, Chun-Hui; Israel, Matthew; Hu, Qiao-Sheng

2011-01-01

Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1′-spirobiindane-7,7′-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an efficient method to access β-substituted ketones and might lead to the development of other sequential/tandem reactions with transition metal-catalyzed addition reactions as the key step. PMID:21417359

Sequential aldol condensation-transition metal-catalyzed addition reactions of aldehydes, methyl ketones, and arylboronic acids.

PubMed

Liao, Yuan-Xi; Xing, Chun-Hui; Israel, Matthew; Hu, Qiao-Sheng

2011-04-15

Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1'-spirobiindane-7,7'-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an efficient method to access β-substituted ketones and might lead to the development of other sequential/tandem reactions with transition metal-catalyzed addition reactions as the key step. © 2011 American Chemical Society

Sequential infiltration synthesis for enhancing multiple-patterning lithography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darling, Seth B.; Elam, Jeffrey W.; Tseng, Yu-Chih

Simplified methods of multiple-patterning photolithography using sequential infiltration synthesis to modify the photoresist such that it withstands plasma etching better than unmodified resist and replaces one or more hard masks and/or a freezing step in MPL processes including litho-etch-litho-etch photolithography or litho-freeze-litho-etch photolithography.

Probabilistic Guidance of Swarms using Sequential Convex Programming

DTIC Science & Technology

2014-01-01

quadcopter fleet [24]. In this paper, sequential convex programming (SCP) [25] is implemented using model predictive control (MPC) to provide real-time...in order to make Problem 1 convex. The details for convexifying this problem can be found in [26]. The main steps are discretizing the problem using

Poor Performance on Serial Visual Tasks in Persons with Reading Disabilities: Impaired Working Memory?

ERIC Educational Resources Information Center

Ram-Tsur, Ronit; Faust, Miriam; Zivotofsky, Ari Z.

2008-01-01

The present study investigates the performance of persons with reading disabilities (PRD) on a variety of sequential visual-comparison tasks that have different working-memory requirements. In addition, mediating relationships between the sequential comparison process and attention and memory skills were looked for. Our findings suggest that PRD…

Properties of true quaternary fission of nuclei with allowance for its multistep and sequential character

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kadmensky, S. G., E-mail: kadmensky@phys.vsu.ru; Titova, L. V.; Bulychev, A. O.

An analysis of basicmechanisms of binary and ternary fission of nuclei led to the conclusion that true ternary and quaternary fission of nuclei has a sequential two-step (three-step) character, where, at the first step, a fissile nucleus emits a third light particle (third and fourth light particles) under shakeup effects associated with a nonadiabatic character of its collective deformation motion, whereupon the residual nucleus undergoes fission to two fission fragments. Owing to this, the formulas derived earlier for the widths with respect to sequential two- and three-step decays of nuclei in constructing the theory of two-step twoproton decays and multistepmore » decays in chains of genetically related nuclei could be used to describe the relative yields and angular and energy distributions of third and fourth light particles emitted in (α, α), (t, t), and (α, t) pairs upon the true quaternary spontaneous fission of {sup 252}Cf and thermal-neutron-induced fission of {sup 235}U and {sup 233}U target nuclei. Mechanisms that explain a sharp decrease in the yield of particles appearing second in time and entering into the composition of light-particle pairs that originate from true quaternary fission of nuclei in relation to the yields of analogous particles in true ternary fission of nuclei are proposed.« less

Multiple stage miniature stepping motor

DOEpatents

Niven, William A.; Shikany, S. David; Shira, Michael L.

1981-01-01

A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

Volleyball. Steps to Success.

ERIC Educational Resources Information Center

Viera, Barbara L.; Ferguson, Bonnie Jill

This handbook was written to introduce learners to the game of volleyball and its skills and strategies. Twenty-four steps to mastery of techniques of the game are organized sequentially, providing a transition from one skill to the next. An explanation of what is covered in the step, why it is important, and how to execute or perform the step's…

Role of PIN-mediated auxin efflux in apical hook development of Arabidopsis thaliana.

PubMed

Zádníková, Petra; Petrásek, Jan; Marhavy, Peter; Raz, Vered; Vandenbussche, Filip; Ding, Zhaojun; Schwarzerová, Katerina; Morita, Miyo T; Tasaka, Masao; Hejátko, Jan; Van Der Straeten, Dominique; Friml, Jirí; Benková, Eva

2010-02-01

The apical hook of dark-grown Arabidopsis seedlings is a simple structure that develops soon after germination to protect the meristem tissues during emergence through the soil and that opens upon exposure to light. Differential growth at the apical hook proceeds in three sequential steps that are regulated by multiple hormones, principally auxin and ethylene. We show that the progress of the apical hook through these developmental phases depends on the dynamic, asymmetric distribution of auxin, which is regulated by auxin efflux carriers of the PIN family. Several PIN proteins exhibited specific, partially overlapping spatial and temporal expression patterns, and their subcellular localization suggested auxin fluxes during hook development. Genetic manipulation of individual PIN activities interfered with different stages of hook development, implying that specific combinations of PIN genes are required for progress of the apical hook through the developmental phases. Furthermore, ethylene might modulate apical hook development by prolonging the formation phase and strongly suppressing the maintenance phase. This ethylene effect is in part mediated by regulation of PIN-dependent auxin efflux and auxin signaling.

Step-wise refolding of recombinant proteins.

PubMed

Tsumoto, Kouhei; Arakawa, Tsutomu; Chen, Linda

2010-04-01

Protein refolding is still on trial-and-error basis. Here we describe step-wise dialysis refolding, in which denaturant concentration is altered in step-wise fashion. This technology controls the folding pathway by adjusting the concentrations of the denaturant and other solvent additives to induce sequential folding or disulfide formation.

The Rhetorical Cycle: Reading, Thinking, Speaking, Listening, Discussing, Writing.

ERIC Educational Resources Information Center

Keller, Rodney D.

The rhetorical cycle is a step-by-step approach that provides classroom experience before students actually write, thereby making the writing process less frustrating for them. This approach consists of six sequential steps: reading, thinking, speaking, listening, discussing, and finally writing. Readings serve not only as models of rhetorical…

How Does Mentoring Contribute to Gen Y Employees’ Intention to Stay? An Indian Perspective

PubMed Central

Naim, Mohammad Faraz; Lenka, Usha

2017-01-01

The present study is aimed at investigating the impact of mentoring on intention to stay of Gen Y employees working in Indian IT industry. Also, the mediating roles of perceived organization support and affective commitment are examined. Primary data were collected from a sample of 314 Gen Y employees (born between 1980-2000) from IT industry in Delhi, NCR India. Data analysis was carried out using AMOS and SPSS to test sequential mediation. Findings reveal that mentoring has a direct influence on intention to stay of Gen Y employees and perceived organization support and affective commitment sequentially mediate the relationship between the two. This study contributes to the literature on mentoring, perceived organization support, affective commitment, and intention to stay. PMID:28580029

On the mechanism of the palladium catalyzed intramolecular Pauson-Khand-type reaction.

PubMed

Lan, Yu; Deng, Lujiang; Liu, Jing; Wang, Can; Wiest, Olaf; Yang, Zhen; Wu, Yun-Dong

2009-07-17

Density functional theory calculations and experimental studies have been carried out on the intramolecular Pauson-Khand-Type reaction mediated by a PdCl(2)-thiourea catalyst, which proceeds under mild reaction conditions and provides a useful alternative to traditional Pauson-Khand reactions. The classical mechanism of the Pauson-Khand reaction involving the alkyne/alkene C-C bond formation as the key step has been found to be energetically unfavorable and is not in line with the experimental observations. A novel reaction mechanism has been proposed for the reaction. The first step involves the cis-halometalation of the alkyne, followed by sequential alkene and carbonyl insertion. The rate-determining fourth step is an intramolecular C-Cl oxidative addition, leading to a Pd(IV) intermediate. A C-C bond formation by reductive elimination completes the reaction. The mechanism is in agreement with the key experimental observations including (1) the need of a chloride for catalytic activity and the absence of catalysis with Pd(OAc)(2) alone; (2) the rate acceleration by the addition of LiCl; both with PdCl(2) and Pd(OAc)(2) catalysts; and (3) the preferred formation of the trans diastereomer in substituted cases. The cis halometalation and the formation and stability of the Pd(IV) intermediate is studied in detail and provides general insights into these novel steps.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faye, Sherry A.; Richards, Jason M.; Gallardo, Athena M.

Sequential extraction is a useful technique for assessing the potential to leach actinides from soils; however, current literature lacks uniformity in experimental details, making direct comparison of results impossible. This work continued development toward a standardized five-step sequential extraction protocol by analyzing extraction behaviors of 232Th, 238U, 239,240Pu and 241Am from lake and ocean sediment reference materials. Results produced a standardized procedure after creating more defined reaction conditions to improve method repeatability. A NaOH fusion procedure is recommended following sequential leaching for the complete dissolution of insoluble species.

Drosophila Pkaap regulates Rab4/Rab11-dependent traffic and Rab11 exocytosis of innate immune cargo

PubMed Central

Sorvina, Alexandra; Shandala, Tetyana; Brooks, Douglas A.

2016-01-01

ABSTRACT The secretion of immune-mediators is a critical step in the host innate immune response to pathogen invasion, and Rab GTPases have an important role in the regulation of this process. Rab4/Rab11 recycling endosomes are involved in the sorting of immune-mediators into specialist Rab11 vesicles that can traffic this cargo to the plasma membrane; however, how this sequential delivery process is regulated has yet to be fully defined. Here, we report that Drosophila Pkaap, an orthologue of the human dual-specific A-kinase-anchoring protein 2 or D-AKAP2 (also called AKAP10), appeared to have a nucleotide-dependent localisation to Rab4 and Rab11 endosomes. RNAi silencing of pkaap altered Rab4/Rab11 recycling endosome morphology, suggesting that Pkaap functions in cargo sorting and delivery in the secretory pathway. The depletion of pkaap also had a direct effect on Rab11 vesicle exocytosis and the secretion of the antimicrobial peptide Drosomycin at the plasma membrane. We propose that Pkaap has a dual role in antimicrobial peptide traffic and exocytosis, making it an essential component for the secretion of inflammatory mediators and the defence of the host against pathogens. PMID:27190105

Trial-to-Trial Modulations of the Simon Effect in Conditions of Attentional Limitations : Evidence from Dual Tasks

ERIC Educational Resources Information Center

Fischer, Rico; Plessow, Franziska; Kunde, Wilfried; Kiesel, Andrea

2010-01-01

Interference effects are reduced after trials including response conflict. This sequential modulation has often been attributed to a top-down mediated adaptive control mechanism and/or to feature repetition mechanisms. In the present study we tested whether mechanisms responsible for such sequential modulations are subject to attentional…

High precision quantification of human plasma proteins using the automated SISCAPA Immuno-MS workflow.

PubMed

Razavi, Morteza; Leigh Anderson, N; Pope, Matthew E; Yip, Richard; Pearson, Terry W

2016-09-25

Efficient robotic workflows for trypsin digestion of human plasma and subsequent antibody-mediated peptide enrichment (the SISCAPA method) were developed with the goal of improving assay precision and throughput for multiplexed protein biomarker quantification. First, an 'addition only' tryptic digestion protocol was simplified from classical methods, eliminating the need for sample cleanup, while improving reproducibility, scalability and cost. Second, methods were developed to allow multiplexed enrichment and quantification of peptide surrogates of protein biomarkers representing a very broad range of concentrations and widely different molecular masses in human plasma. The total workflow coefficients of variation (including the 3 sequential steps of digestion, SISCAPA peptide enrichment and mass spectrometric analysis) for 5 proteotypic peptides measured in 6 replicates of each of 6 different samples repeated over 6 days averaged 3.4% within-run and 4.3% across all runs. An experiment to identify sources of variation in the workflow demonstrated that MRM measurement and tryptic digestion steps each had average CVs of ∼2.7%. Because of the high purity of the peptide analytes enriched by antibody capture, the liquid chromatography step is minimized and in some cases eliminated altogether, enabling throughput levels consistent with requirements of large biomarker and clinical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Dancing the night away: Improving the persistence of locomotion on the micron scale

NASA Astrophysics Data System (ADS)

Gehrels, Emily W.; Rogers, W. Benjamin; Zeravcic, Zorana; Manoharan, Vinothan N.

In recent years a range of nano and microscale walkers (motors that are able to move along a preformed track) have been developed. Many of these walkers bind to their tracks using a single binding site at each station along the track. A disadvantage of these systems is that any failure involving a single site becoming unbound leads to the walker falling off of the track and locomotion being prematurely terminated. For this reason, it has been difficult to develop a motor that can reliably take more than a few sequential steps. We present an experimental system of DNA-functionalized colloidal particles which exhibit directed motion along patterned substrates in response to temperature cycling. Many DNA bridges form between each pair of interacting particles, adding redundancy to the binding at each station to realize a system that should be able to consistently take many steps. We take advantage of toehold exchange in the design of the DNA sequences that mediate the colloidal interactions to produce broadened, flat, or even re-entrant binding and unbinding transitions between the particles and substrate. Using this new freedom of design, we devise systems where, by thermal ratcheting, we can externally control the direction of motion and sequence of steps of the colloidal motor.

Regeneration of glass nanofluidic chips through a multiple-step sequential thermochemical decomposition process at high temperatures.

PubMed

Xu, Yan; Wu, Qian; Shimatani, Yuji; Yamaguchi, Koji

2015-10-07

Due to the lack of regeneration methods, the reusability of nanofluidic chips is a significant technical challenge impeding the efficient and economic promotion of both fundamental research and practical applications on nanofluidics. Herein, a simple method for the total regeneration of glass nanofluidic chips was described. The method consists of sequential thermal treatment with six well-designed steps, which correspond to four sequential thermal and thermochemical decomposition processes, namely, dehydration, high-temperature redox chemical reaction, high-temperature gasification, and cooling. The method enabled the total regeneration of typical 'dead' glass nanofluidic chips by eliminating physically clogged nanoparticles in the nanochannels, removing chemically reacted organic matter on the glass surface and regenerating permanent functional surfaces of dissimilar materials localized in the nanochannels. The method provides a technical solution to significantly improve the reusability of glass nanofluidic chips and will be useful for the promotion and acceleration of research and applications on nanofluidics.

Electrochemistry at a Metal Nanoparticle on a Tunneling Film: A Steady-State Model of Current Densities at a Tunneling Ultramicroelectrode.

PubMed

Hill, Caleb M; Kim, Jiyeon; Bard, Allen J

2015-09-09

Here, a new methodology is proposed for treating electrochemical current densities in metal-insulator-metal nanoparticle (M-I-MNP) systems. The described model provides broad, practical insights about MNP-mediated electron transfer to redox species in solution, where electron transfer from the underlying electrode to a MNP via tunneling and heterogeneous electron transfer from the MNP to redox species in solution are treated as sequential steps. Tunneling is treated through an adaptation of the Simmons model of tunneling in metal-insulator-metal structures, and explicit equations are provided for tunneling currents, which demonstrate the effect of various experimental parameters, such as insulator thickness and MNP size. Overall, a general approach is demonstrated for determining experimental conditions where tunneling will have a measurable impact on the electrochemistry of M-I-MNP systems.

Sulfur K-edge XANES and acid volatile sulfide analyses of changes in chemical speciation of S and Fe during sequential extraction of trace metals in anoxic sludge from biogas reactors.

PubMed

Shakeri Yekta, Sepehr; Gustavsson, Jenny; Svensson, Bo H; Skyllberg, Ulf

2012-01-30

The effect of sequential extraction of trace metals on sulfur (S) speciation in anoxic sludge samples from two lab-scale biogas reactors augmented with Fe was investigated. Analyses of sulfur K-edge X-ray absorption near edge structure (S XANES) spectroscopy and acid volatile sulfide (AVS) were conducted on the residues from each step of the sequential extraction. The S speciation in sludge samples after AVS analysis was also determined by S XANES. Sulfur was mainly present as FeS (≈ 60% of total S) and reduced organic S (≈ 30% of total S), such as organic sulfide and thiol groups, in the anoxic solid phase. Sulfur XANES and AVS analyses showed that during first step of the extraction procedure (the removal of exchangeable cations), a part of the FeS fraction corresponding to 20% of total S was transformed to zero-valent S, whereas Fe was not released into the solution during this transformation. After the last extraction step (organic/sulfide fraction) a secondary Fe phase was formed. The change in chemical speciation of S and Fe occurring during sequential extraction procedure suggests indirect effects on trace metals associated to the FeS fraction that may lead to incorrect results. Furthermore, by S XANES it was verified that the AVS analysis effectively removed the FeS fraction. The present results identified critical limitations for the application of sequential extraction for trace metal speciation analysis outside the framework for which the methods were developed. Copyright © 2011 Elsevier B.V. All rights reserved.

In situ epoxide generation by dimethyldioxirane oxidation and the use of epichlorohydrin in the flow synthesis of a library of β-amino alcohols.

PubMed

Cossar, Peter J; Baker, Jennifer R; Cain, Nicholas; McCluskey, Adam

2018-04-01

The flow coupling of epichlorohydrin with substituted phenols, while efficient, limits the nature of the epoxide available for the development of focused libraries of β-amino alcohols. This limitation was encountered in the production of analogues of 1-(4-nitrophenoxy)-3-((2-((4-(trifluoromethyl)pyrimidin-2-yl)amino)ethyl)amino)propan-2-ol 1 , a potential antibiotic lead. The in situ (flow) generation of dimethyldoxirane (DMDO) and subsequent flow olefin epoxidation abrogates this limitation and afforded facile access to structurally diverse β-amino alcohols. Analogues of 1 were readily accessed either via (i) a flow/microwave hybrid approach, or (ii) a sequential flow approach. Key steps were the in situ generation of DMDO, with olefin epoxidation in typically good yields and a flow-mediated ring opening aminolysis to form an expanded library of β-amino alcohols 1 and 10a - 18g , resulting in modest ( 11a , 21%) to excellent ( 12g , 80%) yields. Alternatively flow coupling of epichlorohydrin with phenols 4a - 4m (22%-89%) and a Bi(OTf) 3 catalysed microwave ring opening with amines afforded a select range of β-amino alcohols, but with lower levels of aminolysis regiocontrol than the sequential flow approach.

In situ epoxide generation by dimethyldioxirane oxidation and the use of epichlorohydrin in the flow synthesis of a library of β-amino alcohols

PubMed Central

Cossar, Peter J.; Baker, Jennifer R.; Cain, Nicholas

2018-01-01

The flow coupling of epichlorohydrin with substituted phenols, while efficient, limits the nature of the epoxide available for the development of focused libraries of β-amino alcohols. This limitation was encountered in the production of analogues of 1-(4-nitrophenoxy)-3-((2-((4-(trifluoromethyl)pyrimidin-2-yl)amino)ethyl)amino)propan-2-ol 1, a potential antibiotic lead. The in situ (flow) generation of dimethyldoxirane (DMDO) and subsequent flow olefin epoxidation abrogates this limitation and afforded facile access to structurally diverse β-amino alcohols. Analogues of 1 were readily accessed either via (i) a flow/microwave hybrid approach, or (ii) a sequential flow approach. Key steps were the in situ generation of DMDO, with olefin epoxidation in typically good yields and a flow-mediated ring opening aminolysis to form an expanded library of β-amino alcohols 1 and 10a–18g, resulting in modest (11a, 21%) to excellent (12g, 80%) yields. Alternatively flow coupling of epichlorohydrin with phenols 4a–4m (22%–89%) and a Bi(OTf)3 catalysed microwave ring opening with amines afforded a select range of β-amino alcohols, but with lower levels of aminolysis regiocontrol than the sequential flow approach. PMID:29765627

Propagating probability distributions of stand variables using sequential Monte Carlo methods

Treesearch

Jeffrey H. Gove

2009-01-01

A general probabilistic approach to stand yield estimation is developed based on sequential Monte Carlo filters, also known as particle filters. The essential steps in the development of the sampling importance resampling (SIR) particle filter are presented. The SIR filter is then applied to simulated and observed data showing how the 'predictor - corrector'...

Social Cognitive Antecedents of Fruit and Vegetable Consumption in Truck Drivers: A Sequential Mediation Analysis.

PubMed

Hamilton, Kyra; Vayro, Caitlin; Schwarzer, Ralf

2015-01-01

To examine a mechanism by which social cognitive factors may predict fruit and vegetable consumption in long-haul truck drivers. Dietary self-efficacy, positive outcome expectancies, and intentions were assessed in 148 Australian truck drivers, and 1 week later they reported their fruit and vegetable consumption. A theory-guided sequential mediation model was specified that postulated self-efficacy and intention as mediators between outcome expectancies and behavior. The hypothesized model was confirmed. A direct effect of outcome expectancies was no longer present when mediators were included, and all indirect effects were significant, including the 2-mediator chain (β = .15; P < .05; 95% confidence interval, 0.05-0.32). Truck drivers who expected benefits from dietary change, felt confident about being capable to do so, and formed an intention were likely to report larger amounts of fruit and vegetable intake. The results suggest that the role of outcome expectancies and self-efficacy are important to consider for understanding and predicting healthy eating intentions in truck drivers. Copyright © 2015 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

A Sequential Multiplicative Extended Kalman Filter for Attitude Estimation Using Vector Observations.

PubMed

Qin, Fangjun; Chang, Lubin; Jiang, Sai; Zha, Feng

2018-05-03

In this paper, a sequential multiplicative extended Kalman filter (SMEKF) is proposed for attitude estimation using vector observations. In the proposed SMEKF, each of the vector observations is processed sequentially to update the attitude, which can make the measurement model linearization more accurate for the next vector observation. This is the main difference to Murrell’s variation of the MEKF, which does not update the attitude estimate during the sequential procedure. Meanwhile, the covariance is updated after all the vector observations have been processed, which is used to account for the special characteristics of the reset operation necessary for the attitude update. This is the main difference to the traditional sequential EKF, which updates the state covariance at each step of the sequential procedure. The numerical simulation study demonstrates that the proposed SMEKF has more consistent and accurate performance in a wide range of initial estimate errors compared to the MEKF and its traditional sequential forms.

A Sequential Multiplicative Extended Kalman Filter for Attitude Estimation Using Vector Observations

PubMed Central

Qin, Fangjun; Jiang, Sai; Zha, Feng

2018-01-01

In this paper, a sequential multiplicative extended Kalman filter (SMEKF) is proposed for attitude estimation using vector observations. In the proposed SMEKF, each of the vector observations is processed sequentially to update the attitude, which can make the measurement model linearization more accurate for the next vector observation. This is the main difference to Murrell’s variation of the MEKF, which does not update the attitude estimate during the sequential procedure. Meanwhile, the covariance is updated after all the vector observations have been processed, which is used to account for the special characteristics of the reset operation necessary for the attitude update. This is the main difference to the traditional sequential EKF, which updates the state covariance at each step of the sequential procedure. The numerical simulation study demonstrates that the proposed SMEKF has more consistent and accurate performance in a wide range of initial estimate errors compared to the MEKF and its traditional sequential forms. PMID:29751538

Negative affect and smoking motives sequentially mediate the effect of panic attacks on tobacco-relevant processes

PubMed Central

Farris, Samantha G.; Zvolensky, Michael J.; Blalock, Janice A.; Schmidt, Norman B.

2018-01-01

Introduction Empirical work has documented a robust and consistent relation between panic attacks and smoking behavior. Theoretical models posit smokers with panic attacks may rely on smoking to help them manage chronically elevated negative affect due to uncomfortable bodily states, which may explain higher levels of nicotine dependence and quit problems. Methods The current study examined the effects of panic attack history on nicotine dependence, perceived barriers for quitting, smoking inflexibility when emotionally distressed, and expired carbon monoxide among 461 treatment-seeking smokers. A multiple mediator path model was evaluated to examine the indirect effects of negative affect and negative affect reduction motives as mediators of the panic attack-smoking relations. Results Panic attack history was indirectly related to greater levels of nicotine dependence (b=0.039, CI95%=0.008, 0.097), perceived barriers to smoking cessation (b=0.195, CI95%=0.043, 0.479), smoking inflexibility/avoidance when emotionally distressed (b=0.188, CI95%=0.041, 0.445), and higher levels of expired carbon monoxide (b=0.071, CI95%=0.010, 0.230) through the sequential effects of negative affect and negative affect smoking motives. Conclusions The present results provide empirical support for the sequential mediating role of negative affect and smoking motives for negative affect reduction in the relation between panic attacks and a variety of smoking variables in treatment-seeking smokers. These mediating variables are likely important processes to address in smoking cessation treatment, especially in panic-vulnerable smokers. PMID:24720260

Negative affect and smoking motives sequentially mediate the effect of panic attacks on tobacco-relevant processes.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Blalock, Janice A; Schmidt, Norman B

2014-05-01

Empirical work has documented a robust and consistent relation between panic attacks and smoking behavior. Theoretical models posit smokers with panic attacks may rely on smoking to help them manage chronically elevated negative affect due to uncomfortable bodily states, which may explain higher levels of nicotine dependence and quit problems. The current study examined the effects of panic attack history on nicotine dependence, perceived barriers for quitting, smoking inflexibility when emotionally distressed, and expired carbon monoxide among 461 treatment-seeking smokers. A multiple mediator path model was evaluated to examine the indirect effects of negative affect and negative affect reduction motives as mediators of the panic attack-smoking relations. Panic attack history was indirectly related to greater levels of nicotine dependence (b = 0.039, CI95% = 0.008, 0.097), perceived barriers to smoking cessation (b = 0.195, CI95% = 0.043, 0.479), smoking inflexibility/avoidance when emotionally distressed (b = 0.188, CI95% = 0.041, 0.445), and higher levels of expired carbon monoxide (b = 0.071, CI95% = 0.010, 0.230) through the sequential effects of negative affect and negative affect smoking motives. The present results provide empirical support for the sequential mediating role of negative affect and smoking motives for negative affect reduction in the relation between panic attacks and a variety of smoking variables in treatment-seeking smokers. These mediating variables are likely important processes to address in smoking cessation treatment, especially in panic-vulnerable smokers.

Fundamental Study on the Fabrication of Inverted Planar Perovskite Solar Cells Using Two-Step Sequential Substrate Vibration-Assisted Spray Coating (2S-SVASC).

PubMed

Zabihi, Fatemeh; Ahmadian-Yazdi, Mohammad-Reza; Eslamian, Morteza

2016-12-01

In this paper, a scalable and fast process is developed and employed for the fabrication of the perovskite light harvesting layer in inverted planar heterojunction solar cell (FTO/PEDOT:PSS/CH3NH3PbI3-x Cl x /PCBM/Al). Perovskite precursor solutions are sprayed onto an ultrasonically vibrating substrate in two sequential steps via a process herein termed as the two-step sequential substrate vibration-assisted spray coating (2S-SVASC). The gentle imposed ultrasonic vibration on the substrate promotes droplet spreading and coalescence, surface wetting, evaporation, mixing of reagents, and uniform growth of perovskite nanocrystals. The role of the substrate temperature, substrate vibration intensity, and the time interval between the two sequential sprays are studied on the roughness, coverage, and crystalline structure of perovskite thin films. We demonstrate that a combination of a long time interval between spraying of precursor solutions (15 min), a high substrate temperature (120 °C), and a mild substrate vibration power (5 W) results in a favorable morphology and surface quality. The characteristics and performance of prepared perovskite thin films made via the 2S-SVASC technique are compared with those of the co-sprayed perovskite thin films. The maximum power conversion efficiency of 5.08 % on a 0.3-cm(2) active area is obtained for the device made via the scalable 2S-SVASC technique.

Applying Molecular Tools for Monitoring Inhibition of Nitrification by Heavy Metals

EPA Science Inventory

The biological removal of ammonia in conventional wastewater treatment plants (WWTPs) is performed by promoting nitrification and denitrification as sequential steps. The first step in nitrification, the oxidation of ammonia to nitrite by ammonia oxidizing bacteria (AOB), is sens...

Kar5p is required for multiple functions in both inner and outer nuclear envelope fusion in Saccharomyces cerevisiae.

PubMed

Rogers, Jason V; Rose, Mark D

2014-12-02

During mating in the budding yeast Saccharomyces cerevisiae, two haploid nuclei fuse via two sequential membrane fusion steps. SNAREs (i.e., soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Prm3p mediate outer nuclear membrane fusion, but the inner membrane fusogen remains unknown. Kar5p is a highly conserved transmembrane protein that localizes adjacent to the spindle pole body (SPB), mediates nuclear envelope fusion, and recruits Prm3p adjacent to the SPB. To separate Kar5p's functions, we tested localization, Prm3p recruitment, and nuclear fusion efficiency in various kar5 mutants. All domains and the conserved cysteine residues were essential for nuclear fusion. Several kar5 mutant proteins localized properly but did not mediate Prm3p recruitment; other kar5 mutant proteins localized and recruited Prm3p but were nevertheless defective for nuclear fusion, demonstrating additional functions beyond Prm3p recruitment. We identified one Kar5p domain required for SPB localization, which is dependent on the half-bridge protein Mps3p. Electron microscopy revealed a kar5 mutant that arrests with expanded nuclear envelope bridges, suggesting that Kar5p is required after outer nuclear envelope fusion. Finally, a split-GFP assay demonstrated that Kar5p localizes to both the inner and outer nuclear envelope. These insights suggest a mechanism by which Kar5p mediates inner nuclear membrane fusion. Copyright © 2015 Rogers and Rose.

Kar5p Is Required for Multiple Functions in Both Inner and Outer Nuclear Envelope Fusion in Saccharomyces cerevisiae

PubMed Central

Rogers, Jason V.; Rose, Mark D.

2014-01-01

During mating in the budding yeast Saccharomyces cerevisiae, two haploid nuclei fuse via two sequential membrane fusion steps. SNAREs (i.e., soluble N-ethylmaleimide–sensitive factor attachment protein receptors) and Prm3p mediate outer nuclear membrane fusion, but the inner membrane fusogen remains unknown. Kar5p is a highly conserved transmembrane protein that localizes adjacent to the spindle pole body (SPB), mediates nuclear envelope fusion, and recruits Prm3p adjacent to the SPB. To separate Kar5p’s functions, we tested localization, Prm3p recruitment, and nuclear fusion efficiency in various kar5 mutants. All domains and the conserved cysteine residues were essential for nuclear fusion. Several kar5 mutant proteins localized properly but did not mediate Prm3p recruitment; other kar5 mutant proteins localized and recruited Prm3p but were nevertheless defective for nuclear fusion, demonstrating additional functions beyond Prm3p recruitment. We identified one Kar5p domain required for SPB localization, which is dependent on the half-bridge protein Mps3p. Electron microscopy revealed a kar5 mutant that arrests with expanded nuclear envelope bridges, suggesting that Kar5p is required after outer nuclear envelope fusion. Finally, a split-GFP assay demonstrated that Kar5p localizes to both the inner and outer nuclear envelope. These insights suggest a mechanism by which Kar5p mediates inner nuclear membrane fusion. PMID:25467943

Three-Dimensions vs. Two-Dimensions Intervention Programs: The Effect on the Mediation Level and Behavioural Aspects of Children with Intellectual Disability

ERIC Educational Resources Information Center

Eden, S.; Bezer, M.

2011-01-01

The research examined the effect of an intervention program employing 3D immersive virtual reality (IVR), which focused on the perception of sequential time, on the mediation level and behavioural aspects of children with intellectual disability (ID). The intervention is based on the mediated learning experience (MLE) theory, which refers the…

A multistep general theory of transition to addiction.

PubMed

Piazza, Pier Vincenzo; Deroche-Gamonet, Véronique

2013-10-01

Several theories propose alternative explanations for drug addiction. We propose a general theory of transition to addiction that synthesizes knowledge generated in the field of addiction into a unitary explanatory frame. Transition to addiction results from a sequential three-step interaction between: (1) individual vulnerability; (2) degree/amount of drug exposure. The first step, sporadic recreational drug use is a learning process mediated by overactivation of neurobiological substrates of natural rewards that allows most individuals to perceive drugs as highly rewarding stimuli. The second, intensified, sustained, escalated drug use occurs in some vulnerable individuals who have a hyperactive dopaminergic system and impaired prefrontal cortex function. Sustained and prolonged drug use induces incentive sensitization and an allostatic state that makes drugs strongly wanted and needed. Habit formation can also contribute to stabilizing sustained drug use. The last step, loss of control of drug intake and full addiction, is due to a second vulnerable phenotype. This loss-of-control-prone phenotype is triggered by long-term drug exposure and characterized by long-lasting loss of synaptic plasticity in reward areas in the brain that induce a form of behavioral crystallization resulting in loss of control of drug intake. Because of behavioral crystallization, drugs are now not only wanted and needed but also pathologically mourned when absent. This general theory demonstrates that drug addiction is a true psychiatric disease caused by a three-step interaction between vulnerable individuals and amount/duration of drug exposure.

Sequential pH-dependent adsorption of ionic amphiphilic diblock copolymer micelles and choline oxidase onto conductive substrates: toward the design of biosensors.

PubMed

Sigolaeva, Larisa V; Günther, Ulrike; Pergushov, Dmitry V; Gladyr, Snezhana Yu; Kurochkin, Ilya N; Schacher, Felix H

2014-07-01

This work examines the fabrication regime and the properties of polymer-enzyme thin-films adsorbed onto conductive substrates (graphite or gold). The films are formed via two-steps, sequential adsorption of poly(n-butylmethacrylate)-block-poly(N,N-dimethylaminoethyl methacrylate) (PnBMA-b-PDMAEMA) diblock copolymer micelles (1st step of adsorption), followed by the enzyme choline oxidase (ChO) (2nd step of adsorption). The solution properties of both adsorbed components are studied and the pH-dependent step-by-step fabrication of polymer-enzyme biosensor coatings reveals rather drastic differences in their enzymatic activities in dependence on the pH of both adsorption steps. The resulting hybrid thin-films represent highly active biosensors for choline with a low detection limit of 30 nM and a good linearity in a range between 30 nM and 100 μM. The sensitivity is found to be 175 μA mM(-1) cm(-2) and the operational stability of the polymer-enzyme thin-films can be additionally improved via enzyme-to-enzyme crosslinking with glutaraldehyde. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation of Term Papers Based upon a Research-Process Model.

ERIC Educational Resources Information Center

Feldmann, Rodney Mansfield; Schloman, Barbara Frick

1990-01-01

Described is an alternative method of term paper preparation which provides a step-by-step sequence of assignments and provides feedback to the students at all stages in the preparation of the report. An example of this model is provided including 13 sequential assignments. (CW)

Post-processing techniques to enhance reliability of assignment algorithm based performance measures : [technical summary].

DOT National Transportation Integrated Search

2011-01-01

Travel demand modeling plays a key role in the transportation system planning and evaluation process. The four-step sequential travel demand model is the most widely used technique in practice. Traffic assignment is the key step in the conventional f...

Time scale of random sequential adsorption.

PubMed

Erban, Radek; Chapman, S Jonathan

2007-04-01

A simple multiscale approach to the diffusion-driven adsorption from a solution to a solid surface is presented. The model combines two important features of the adsorption process: (i) The kinetics of the chemical reaction between adsorbing molecules and the surface and (ii) geometrical constraints on the surface made by molecules which are already adsorbed. The process (i) is modeled in a diffusion-driven context, i.e., the conditional probability of adsorbing a molecule provided that the molecule hits the surface is related to the macroscopic surface reaction rate. The geometrical constraint (ii) is modeled using random sequential adsorption (RSA), which is the sequential addition of molecules at random positions on a surface; one attempt to attach a molecule is made per one RSA simulation time step. By coupling RSA with the diffusion of molecules in the solution above the surface the RSA simulation time step is related to the real physical time. The method is illustrated on a model of chemisorption of reactive polymers to a virus surface.

Combined techniques for characterising pasta structure reveals how the gluten network slows enzymic digestion rate.

PubMed

Zou, Wei; Sissons, Mike; Gidley, Michael J; Gilbert, Robert G; Warren, Frederick J

2015-12-01

The aim of the present study is to characterise the influence of gluten structure on the kinetics of starch hydrolysis in pasta. Spaghetti and powdered pasta were prepared from three different cultivars of durum semolina, and starch was also purified from each cultivar. Digestion kinetic parameters were obtained through logarithm-of-slope analysis, allowing identification of sequential digestion steps. Purified starch and semolina were digested following a single first-order rate constant, while pasta and powdered pasta followed two sequential first-order rate constants. Rate coefficients were altered by pepsin hydrolysis. Confocal microscopy revealed that, following cooking, starch granules were completely swollen for starch, semolina and pasta powder samples. In pasta, they were completely swollen in the external regions, partially swollen in the intermediate region and almost intact in the pasta strand centre. Gluten entrapment accounts for sequential kinetic steps in starch digestion of pasta; the compact microstructure of pasta also reduces digestion rates. Copyright © 2015 Elsevier Ltd. All rights reserved.

SSME propellant path leak detection real-time

NASA Technical Reports Server (NTRS)

Crawford, R. A.; Smith, L. M.

1994-01-01

Included are four documents that outline the technical aspects of the research performed on NASA Grant NAG8-140: 'A System for Sequential Step Detection with Application to Video Image Processing'; 'Leak Detection from the SSME Using Sequential Image Processing'; 'Digital Image Processor Specifications for Real-Time SSME Leak Detection'; and 'A Color Change Detection System for Video Signals with Applications to Spectral Analysis of Rocket Engine Plumes'.

DyNAVacS: an integrative tool for optimized DNA vaccine design.

PubMed

Harish, Nagarajan; Gupta, Rekha; Agarwal, Parul; Scaria, Vinod; Pillai, Beena

2006-07-01

DNA vaccines have slowly emerged as keystones in preventive immunology due to their versatility in inducing both cell-mediated as well as humoral immune responses. The design of an efficient DNA vaccine, involves choice of a suitable expression vector, ensuring optimal expression by codon optimization, engineering CpG motifs for enhancing immune responses and providing additional sequence signals for efficient translation. DyNAVacS is a web-based tool created for rapid and easy design of DNA vaccines. It follows a step-wise design flow, which guides the user through the various sequential steps in the design of the vaccine. Further, it allows restriction enzyme mapping, design of primers spanning user specified sequences and provides information regarding the vectors currently used for generation of DNA vaccines. The web version uses Apache HTTP server. The interface was written in HTML and utilizes the Common Gateway Interface scripts written in PERL for functionality. DyNAVacS is an integrated tool consisting of user-friendly programs, which require minimal information from the user. The software is available free of cost, as a web based application at URL: http://miracle.igib.res.in/dynavac/.

Toward a Better Understanding of Student Perceptions of Writing Feedback: A Mixed Methods Study

ERIC Educational Resources Information Center

Zumbrunn, Sharon; Marrs, Sarah; Mewborn, Caitlin

2016-01-01

This explanatory sequential mixed methods study investigated the writing feedback perceptions of middle and high school students (N = 598). The predictive and mediational roles of writing self-efficacy and perceptions of writing feedback on student writing self-regulation aptitude were examined using mediation regression analysis. To augment the…

Sequential character of low-energy ternary and quaternary nuclear fission

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kadmensky, S. G., E-mail: kadmensky@phys.vsu.ru; Bulychev, A. O.

2016-09-15

An analysis of low-energy true ternary (quaternary) nuclear fission leads to the conclusion that these fission modes have a sequential two-step (three-step) character such that the emission of a third particle (third and fourth particles) and the separation of fission fragments occur at distinctly different instants, in contrast to the simultaneous emergence of all fission products in the case of onestep ternary (quaternary) fission. This conclusion relies on the following arguments. First, the emission of a third particle (third and fourth particles) from a fissile nucleus is due to a nonevaporative mechanism associated with a nonadiabatic character of the collectivemore » deformation motion of this nucleus at the stages preceding its scission. Second, the axial symmetry of the deformed fissile compound nucleus and the direction of its symmetry axis both remain unchanged at all stages of ternary (quaternary) fission. This circumstancemakes it possible to explain themechanism of the appearance of observed anisotropies and T — odd asymmeries in the angular distributions of products of ternary (quaternary) nuclear fission. Third, the T —odd asymmetry discovered experimentally in ternary nuclear fission induced by cold polarized neutrons obeys the T —invariance condition only in the case of a sequential two-step (three-step) character of true ternary (quaternary) nuclear fission. At the same time, this asymmetry is not a T —invariant quantity in the case of the simultaneous emission of products of true ternary (quaternary) nuclear fission from the fissile compound nucleus.« less

Multi-objective design optimization of antenna structures using sequential domain patching with automated patch size determination

NASA Astrophysics Data System (ADS)

Koziel, Slawomir; Bekasiewicz, Adrian

2018-02-01

In this article, a simple yet efficient and reliable technique for fully automated multi-objective design optimization of antenna structures using sequential domain patching (SDP) is discussed. The optimization procedure according to SDP is a two-step process: (i) obtaining the initial set of Pareto-optimal designs representing the best possible trade-offs between considered conflicting objectives, and (ii) Pareto set refinement for yielding the optimal designs at the high-fidelity electromagnetic (EM) simulation model level. For the sake of computational efficiency, the first step is realized at the level of a low-fidelity (coarse-discretization) EM model by sequential construction and relocation of small design space segments (patches) in order to create a path connecting the extreme Pareto front designs obtained beforehand. The second stage involves response correction techniques and local response surface approximation models constructed by reusing EM simulation data acquired in the first step. A major contribution of this work is an automated procedure for determining the patch dimensions. It allows for appropriate selection of the number of patches for each geometry variable so as to ensure reliability of the optimization process while maintaining its low cost. The importance of this procedure is demonstrated by comparing it with uniform patch dimensions.

Brief Lags in Interrupted Sequential Performance: Evaluating a Model and Model Evaluation Method

DTIC Science & Technology

2015-01-05

rehearsal mechanism in the model. To evaluate the model we developed a simple new goodness-of-fit test based on analysis of variance that offers an...repeated step). Sequen- tial constraints are common in medicine, equipment maintenance, computer programming and technical support, data analysis ...legal analysis , accounting, and many other home and workplace environ- ments. Sequential constraints also play a role in such basic cognitive processes

Sequential design of discrete linear quadratic regulators via optimal root-locus techniques

NASA Technical Reports Server (NTRS)

Shieh, Leang S.; Yates, Robert E.; Ganesan, Sekar

1989-01-01

A sequential method employing classical root-locus techniques has been developed in order to determine the quadratic weighting matrices and discrete linear quadratic regulators of multivariable control systems. At each recursive step, an intermediate unity rank state-weighting matrix that contains some invariant eigenvectors of that open-loop matrix is assigned, and an intermediate characteristic equation of the closed-loop system containing the invariant eigenvalues is created.

Analyzing Communication Architectures Using Commercial Off-The-Shelf (COTS) Modeling and Simulation Tools

DTIC Science & Technology

1998-06-01

4] By 2010, we should be able to change how we conduct the most intense joint operations. Instead of relying on massed forces and sequential ...not independent, sequential steps. Data probes to support the analysis phase were required to complete the logical models. This generated a need...Networks) Identify Granularity (System Level) - Establish Physical Bounds or Limits to Systems • Determine System Test Configuration and Lineup

A novel sequential process for remediating rare-earth wastewater.

PubMed

Cui, Mingcan; Jang, Min; Kang, Kyounglim; Kim, Dukmin; Snyder, Shane A; Khim, Jeehyeong

2016-02-01

A novel and economic sequential process consisting of precipitation, adsorption, and oxidation was developed to remediate actual rare-earth (RE) wastewater containing various toxic pollutants, including radioactive species. In the precipitation step, porous air stones (PAS) containing waste oyster shell (WOS), PASWOS, was prepared and used to precipitate most heavy metals with >97% removal efficiencies. The SEM-EDS analysis revealed that PAS plays a key role in preventing the surface coating of precipitants on the surface of WOS and in releasing the dissolved species of WOS successively. For the adsorption step, a polyurethane (PU) impregnated by coal mine drainage sludge (CMDS), PUCMDS, was synthesized and applied to deplete fluoride (F), arsenic (As), uranium (U), and thorium (Th) that remained after precipitation. The continuous-mode sequential process using PAS(WOS), PU(CMDS), and ozone (O3) had 99.9-100% removal efficiencies of heavy metals, 99.3-99.9% of F and As, 95.8-99.4% of U and Th, and 92.4% of COD(Cr) for 100 days. The sequential process can treat RE wastewater economically and effectively without stirred-tank reactors, pH controller, continuous injection of chemicals, and significant sludge generation, as well as the quality of the outlet met the EPA recommended limits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functionalized Anodic Aluminum Oxide Membrane–Electrode System for Enzyme Immobilization

PubMed Central

2015-01-01

A nanoporous membrane system with directed flow carrying reagents to sequentially attached enzymes to mimic nature’s enzyme complex system was demonstrated. Genetically modified glycosylation enzyme, OleD Loki variant, was immobilized onto nanometer-scale electrodes at the pore entrances/exits of anodic aluminum oxide membranes through His6-tag affinity binding. The enzyme activity was assessed in two reactions—a one-step “reverse” sugar nucleotide formation reaction (UDP-Glc) and a two-step sequential sugar nucleotide formation and sugar nucleotide-based glycosylation reaction. For the one-step reaction, enzyme specific activity of 6–20 min–1 on membrane supports was seen to be comparable to solution enzyme specific activity of 10 min–1. UDP-Glc production efficiencies as high as 98% were observed at a flow rate of 0.5 mL/min, at which the substrate residence time over the electrode length down pore entrances was matched to the enzyme activity rate. This flow geometry also prevented an unwanted secondary product hydrolysis reaction, as observed in the test homogeneous solution. Enzyme utilization increased by a factor of 280 compared to test homogeneous conditions due to the continuous flow of fresh substrate over the enzyme. To mimic enzyme complex systems, a two-step sequential reaction using OleD Loki enzyme was performed at membrane pore entrances then exits. After UDP-Glc formation at the entrance electrode, aglycon 4-methylumbelliferone was supplied at the exit face of the reactor, affording overall 80% glycosylation efficiency. The membrane platform showed the ability to be regenerated with purified enzyme as well as directly from expression crude, thus demonstrating a single-step immobilization and purification process. PMID:25025628

A Particle Smoother with Sequential Importance Resampling for soil hydraulic parameter estimation: A lysimeter experiment

NASA Astrophysics Data System (ADS)

Montzka, Carsten; Hendricks Franssen, Harrie-Jan; Moradkhani, Hamid; Pütz, Thomas; Han, Xujun; Vereecken, Harry

2013-04-01

An adequate description of soil hydraulic properties is essential for a good performance of hydrological forecasts. So far, several studies showed that data assimilation could reduce the parameter uncertainty by considering soil moisture observations. However, these observations and also the model forcings were recorded with a specific measurement error. It seems a logical step to base state updating and parameter estimation on observations made at multiple time steps, in order to reduce the influence of outliers at single time steps given measurement errors and unknown model forcings. Such outliers could result in erroneous state estimation as well as inadequate parameters. This has been one of the reasons to use a smoothing technique as implemented for Bayesian data assimilation methods such as the Ensemble Kalman Filter (i.e. Ensemble Kalman Smoother). Recently, an ensemble-based smoother has been developed for state update with a SIR particle filter. However, this method has not been used for dual state-parameter estimation. In this contribution we present a Particle Smoother with sequentially smoothing of particle weights for state and parameter resampling within a time window as opposed to the single time step data assimilation used in filtering techniques. This can be seen as an intermediate variant between a parameter estimation technique using global optimization with estimation of single parameter sets valid for the whole period, and sequential Monte Carlo techniques with estimation of parameter sets evolving from one time step to another. The aims are i) to improve the forecast of evaporation and groundwater recharge by estimating hydraulic parameters, and ii) to reduce the impact of single erroneous model inputs/observations by a smoothing method. In order to validate the performance of the proposed method in a real world application, the experiment is conducted in a lysimeter environment.

The Long-Term Effectiveness of the Family Check-up on Peer Preference: Parent-Child Interaction and Child Effortful Control as Sequential Mediators.

PubMed

Chang, Hyein; Shaw, Daniel S; Shelleby, Elizabeth C; Dishion, Thomas J; Wilson, Melvin N

2017-05-01

We examined the longitudinal effects of the Family Check-Up (FCU) intervention beginning in toddlerhood on children's peer preference at school-age. Specifically, a sequential mediational model was proposed in which the FCU was hypothesized to promote peer preference (i.e., higher acceptance and lower rejection by peers) in middle childhood through its positive effects on parent-child interaction and child effortful control in early childhood. Participants were 731 low-income families (49 % female). Qualities of parent-child interaction were observed during structured activities at 2 to 5 years, child effortful control was assessed using behavioral tasks at 5 years, and peer acceptance and rejection were rated by teachers at 7.5 to 10.5 years. Results indicated that the FCU indirectly predicted peer preference by sequentially improving parent-child interaction and child effortful control. The findings are discussed with respect to implications for understanding mechanisms by which early parenting-focused programs may enhance child functioning across time and context.

The Long-Term Effectiveness of the Family Check-up on Peer Preference: Parent-Child Interaction and Child Effortful Control as Sequential Mediators

PubMed Central

Shaw, Daniel S.; Shelleby, Elizabeth C.; Dishion, Thomas J.; Wilson, Melvin N.

2018-01-01

We examined the longitudinal effects of the Family Check-Up (FCU) intervention beginning in toddlerhood on children’s peer preference at school-age. Specifically, a sequential mediational model was proposed in which the FCU was hypothesized to promote peer preference (i.e., higher acceptance and lower rejection by peers) in middle childhood through its positive effects on parent-child interaction and child effortful control in early childhood. Participants were 731 low-income families (49 % female). Qualities of parent-child interaction were observed during structured activities at 2 to 5 years, child effortful control was assessed using behavioral tasks at 5 years, and peer acceptance and rejection were rated by teachers at 7.5 to 10.5 years. Results indicated that the FCU indirectly predicted peer preference by sequentially improving parent-child interaction and child effortful control. The findings are discussed with respect to implications for understanding mechanisms by which early parenting-focused programs may enhance child functioning across time and context. PMID:27558394

"Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Santa Cruz, Gustavo A; Trivillin, Verónica A; Schwint, Amanda E

2011-04-01

In the present study the therapeutic effect and potential toxicity of the novel "Sequential" boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential" BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential" BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ± 2% and 91 ± 3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ± 5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ± 12% and 60 ± 22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential" BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue. © 2011 by Radiation Research Society

Abusive Supervision by Academic Supervisors and Postgraduate Research Students' Creativity: The Mediating Role of Leader-Member Exchange and Intrinsic Motivation

ERIC Educational Resources Information Center

Meng, Yi; Tan, Jing; Li, Jing

2017-01-01

Drawing upon the componential theory of creativity, cognitive evaluation theory and social exchange theory, the study reported in this paper tested a mediating model based on the hypothesis that abusive supervision negatively influences creativity sequentially through leader-member exchange (LMX) and intrinsic motivation. The study employed…

A Guide to Analyzing Message-Response Sequences and Group Interaction Patterns in Computer-Mediated Communication

ERIC Educational Resources Information Center

Jeong, Allan

2005-01-01

This paper proposes a set of methods and a framework for evaluating, modeling, and predicting group interactions in computer-mediated communication. The method of sequential analysis is described along with specific software tools and techniques to facilitate the analysis of message-response sequences. In addition, the Dialogic Theory and its…

Maternal Mind-Mindedness and Children's School Readiness: A Longitudinal Study of Developmental Processes

ERIC Educational Resources Information Center

Bernier, Annie; McMahon, Catherine A.; Perrier, Rachel

2017-01-01

This study aimed to test a 5-wave sequential mediation model linking maternal mind-mindedness during infancy to children's school readiness in kindergarten through a serial mediation involving child language and effortful control in toddlerhood and the preschool years. Among a sample of 204 mother-child dyads, we assessed maternal mind-mindedness…

Method for sequentially processing a multi-level interconnect circuit in a vacuum chamber

NASA Technical Reports Server (NTRS)

Routh, D. E.; Sharma, G. C. (Inventor)

1982-01-01

The processing of wafer devices to form multilevel interconnects for microelectronic circuits is described. The method is directed to performing the sequential steps of etching the via, removing the photo resist pattern, back sputtering the entire wafer surface and depositing the next layer of interconnect material under common vacuum conditions without exposure to atmospheric conditions. Apparatus for performing the method includes a vacuum system having a vacuum chamber in which wafers are processed on rotating turntables. The vacuum chamber is provided with an RF sputtering system and a DC magnetron sputtering system. A gas inlet is provided in the chamber for the introduction of various gases to the vacuum chamber and the creation of various gas plasma during the sputtering steps.

RBS Career Education. Evaluation Planning Manual. Education Is Going to Work.

ERIC Educational Resources Information Center

Kershner, Keith M.

Designed for use with the Research for Better Schools career education program, this evaluation planning manual focuses on procedures and issues central to planning the evaluation of an educational program. Following a statement on the need for evaluation, nine sequential steps for evaluation planning are discussed. The first two steps, program…

Production of DagA and ethanol by sequential utilization of sugars in a mixed-sugar medium simulating microalgal hydrolysate.

PubMed

Park, Juyi; Hong, Soon-Kwang; Chang, Yong Keun

2015-09-01

A novel two-step fermentation process using a mixed-sugar medium mimicking microalgal hydrolysate has been proposed to avoid glucose repression and thus to maximize substrate utilization efficiency. When DagA, a β-agarase was produced in one step in the mixed-sugar medium by using a recombinant Streptomyces lividans, glucose was found to have negative effects on the consumption of the other sugars and DagA biosynthesis causing low substrate utilization efficiency and low DagA productivity. To overcome such difficulties, a new strategy of sequential substrate utilization was developed. In the first step, glucose was consumed by Saccharomyces cerevisiae together with galactose and mannose producing ethanol, after which DagA was produced from the remaining sugars of xylose, rhamnose and ribose. Fucose was not consumed. By adopting this two-step process, the overall substrate utilization efficiency was increased approximately 3-fold with a nearly 2-fold improvement of DagA production, let alone the additional benefit of ethanol production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diagnostic value of tendon thickness and structure in the sonographic diagnosis of supraspinatus tendinopathy: room for a two-step approach.

PubMed

Arend, Carlos Frederico; Arend, Ana Amalia; da Silva, Tiago Rodrigues

2014-06-01

The aim of our study was to systematically compare different methodologies to establish an evidence-based approach based on tendon thickness and structure for sonographic diagnosis of supraspinatus tendinopathy when compared to MRI. US was obtained from 164 symptomatic patients with supraspinatus tendinopathy detected at MRI and 42 asymptomatic controls with normal MRI. Diagnostic yield was calculated for either maximal supraspinatus tendon thickness (MSTT) and tendon structure as isolated criteria and using different combinations of parallel and sequential testing at US. Chi-squared tests were performed to assess sensitivity, specificity, and accuracy of different diagnostic approaches. Mean MSTT was 6.68 mm in symptomatic patients and 5.61 mm in asymptomatic controls (P<.05). When used as an isolated criterion, MSTT>6.0mm provided best results for accuracy (93.7%) when compared to other measurements of tendon thickness. Also as an isolated criterion, abnormal tendon structure (ATS) yielded 93.2% accuracy for diagnosis. The best overall yield was obtained by both parallel and sequential testing using either MSTT>6.0mm or ATS as diagnostic criteria at no particular order, which provided 99.0% accuracy, 100% sensitivity, and 95.2% specificity. Among these parallel and sequential tests that provided best overall yield, additional analysis revealed that sequential testing first evaluating tendon structure required assessment of 258 criteria (vs. 261 for sequential testing first evaluating tendon thickness and 412 for parallel testing) and demanded a mean of 16.1s to assess diagnostic criteria and reach the diagnosis (vs. 43.3s for sequential testing first evaluating tendon thickness and 47.4s for parallel testing). We found that using either MSTT>6.0mm or ATS as diagnostic criteria for both parallel and sequential testing provides the best overall yield for sonographic diagnosis of supraspinatus tendinopathy when compared to MRI. Among these strategies, a two-step sequential approach first assessing tendon structure was advantageous because it required a lower number of criteria to be assessed and demanded less time to assess diagnostic criteria and reach the diagnosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Sequential decision tree using the analytic hierarchy process for decision support in rectal cancer.

PubMed

Suner, Aslı; Çelikoğlu, Can Cengiz; Dicle, Oğuz; Sökmen, Selman

2012-09-01

The aim of the study is to determine the most appropriate method for construction of a sequential decision tree in the management of rectal cancer, using various patient-specific criteria and treatments such as surgery, chemotherapy, and radiotherapy. An analytic hierarchy process (AHP) was used to determine the priorities of variables. Relevant criteria used in two decision steps and their relative priorities were established by a panel of five general surgeons. Data were collected via a web-based application and analyzed using the "Expert Choice" software specifically developed for the AHP. Consistency ratios in the AHP method were calculated for each set of judgments, and the priorities of sub-criteria were determined. A sequential decision tree was constructed for the best treatment decision process, using priorities determined by the AHP method. Consistency ratios in the AHP method were calculated for each decision step, and the judgments were considered consistent. The tumor-related criterion "presence of perforation" (0.331) and the patient-surgeon-related criterion "surgeon's experience" (0.630) had the highest priority in the first decision step. In the second decision step, the tumor-related criterion "the stage of the disease" (0.230) and the patient-surgeon-related criterion "surgeon's experience" (0.281) were the paramount criteria. The results showed some variation in the ranking of criteria between the decision steps. In the second decision step, for instance, the tumor-related criterion "presence of perforation" was just the fifth. The consistency of decision support systems largely depends on the quality of the underlying decision tree. When several choices and variables have to be considered in a decision, it is very important to determine priorities. The AHP method seems to be effective for this purpose. The decision algorithm developed by this method is more realistic and will improve the quality of the decision tree. Copyright © 2012 Elsevier B.V. All rights reserved.

Solving the infeasible trust-region problem using approximations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renaud, John E.; Perez, Victor M.; Eldred, Michael Scott

2004-07-01

The use of optimization in engineering design has fueled the development of algorithms for specific engineering needs. When the simulations are expensive to evaluate or the outputs present some noise, the direct use of nonlinear optimizers is not advisable, since the optimization process will be expensive and may result in premature convergence. The use of approximations for both cases is an alternative investigated by many researchers including the authors. When approximations are present, a model management is required for proper convergence of the algorithm. In nonlinear programming, the use of trust-regions for globalization of a local algorithm has been provenmore » effective. The same approach has been used to manage the local move limits in sequential approximate optimization frameworks as in Alexandrov et al., Giunta and Eldred, Perez et al. , Rodriguez et al., etc. The experience in the mathematical community has shown that more effective algorithms can be obtained by the specific inclusion of the constraints (SQP type of algorithms) rather than by using a penalty function as in the augmented Lagrangian formulation. The presence of explicit constraints in the local problem bounded by the trust region, however, may have no feasible solution. In order to remedy this problem the mathematical community has developed different versions of a composite steps approach. This approach consists of a normal step to reduce the amount of constraint violation and a tangential step to minimize the objective function maintaining the level of constraint violation attained at the normal step. Two of the authors have developed a different approach for a sequential approximate optimization framework using homotopy ideas to relax the constraints. This algorithm called interior-point trust-region sequential approximate optimization (IPTRSAO) presents some similarities to the two normal-tangential steps algorithms. In this paper, a description of the similarities is presented and an expansion of the two steps algorithm is presented for the case of approximations.« less

Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, MiRan; Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr

Ultraviolet (UV) radiation induces cyclooxygenase-2 expression to produce cellular responses including aging and carcinogenesis in skin. We hypothesised that heterotrimeric G proteins mediate UV-induced COX-2 expression by stimulating secretion of soluble HB-EGF (sHB-EGF). In this study, we aimed to elucidate the role and underlying mechanism of the {alpha} subunit of Gq protein (G{alpha}q) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active G{alpha}q (G{alpha}qQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of G{alpha}q with shRNA in HaCaT human keratinocytes. G{alpha}q was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipasemore » C (PLC), protein kinase C{delta} (PKC{delta}), and matrix metaloprotease-2 (MMP-2). Moreover, G{alpha}qQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that G{alpha}q mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKC{delta} and MMP-2 in HaCaT cells.« less

Sequential administration of arginine and arginine plus GHRH to test somatotroph function in short children.

PubMed

Bellone, J; Aimaretti, G; Bellone, S; Baffoni, C; Corneli, G; Origlia, C; Cappa, M; Ghigo, E

2000-02-01

The hormonal diagnosis of GH deficiency in childhood is conventionally based on the GH response to at least two provocative stimuli. Among these, arginine (ARG) has long been considered a classical, centrally mediated stimulus of GH secretion. ARG is also able to potentiate the GH response to GHRH, likely inhibiting hypothalamic somatostatin; this combined test is one of the most potent to explore the maximal secretory capacity of somatotroph cells. Based on these premises, we verified whether the sequential administration of ARG and ARG+GHRH could be feasible as single step provocative test to evaluate the GH releasable pool in short children. To this goal, 48 normal short children (35 M and 13 F, 12.0+/-0.4 yr, PS 1: 255 II-IV: 23) underwent a test with ARG (0.5 g/kg i.v. from 0 to +30 min) followed by a coadministration of ARG (from +120 to 150 min) plus GHRH (1 microg/kg i.v. at +120 min). ARG alone elicited a clear GH response (mean peak vs baseline: 12.1+/-1.7 vs 2.0+/-0.4 microg/l, p<0.001, Cmax range 12-51.0 microg/l). Following this GH rise, the hormonal levels at +120 min approached to baseline levels (4.2+/-0.8 microg/l) but then showed marked response to the coadministration of ARG+GHRH. The GH peak following ARG+GHRH (mean peak: 47.8+/-3.3 microg/l, p<0.001; Cmax 22.4-150.0 microg/l) was clearly higher (p<0.001) than that recorded after ARG alone. The GH responses to both ARG and ARG+GHRH were independent of gender, puberty, height velocity, body mass index (BMI) and IGF-I levels. Nine normal short children (16%) had GH peaks lower than 7 microg/l after ARG alone, while none showed GH peak below 20 microg/l after ARG+GHRH. Thus, ARG alone is a good stimulus of GH secretion but false positive responses frequently occur in normal short children. ARG+GHRH is a more potent stimulus giving no false positive responses even after previous challenge with ARG alone. Testing with sequential administration of ARG and ARG+GHRH may allow the single step evaluation of the somatotroph response to central and pituitary stimuli in short children.

Malpractice and medical liability. European Guidelines on Methods of Ascertainment and Criteria of Evaluation.

PubMed

Ferrara, Santo Davide; Baccino, Eric; Bajanowski, Thomas; Boscolo-Berto, Rafael; Castellano, Maria; De Angel, Ricardo; Pauliukevičius, Alvydas; Ricci, Pietrantonio; Vanezis, Peter; Vieira, Duarte Nuno; Viel, Guido; Villanueva, Enrique

2013-05-01

The manuscript presents the European Guidelines on medico-legal Methods of Ascertainment and Criteria of Evaluation in cases of suspected subjective "Medical Responsibility and/or Liability" developed by an international working group under the patronage of the European Academy of Legal Medicine. It includes a step-by-step illustrated explanation of approved Flow Charts, articulated in 18 sequential steps and comprehensive of both Methods of Ascertainment and Evaluation Criteria.

Magnetoresponsive discoidal photonic crystals toward active color pigments.

PubMed

Lee, Hye Soo; Kim, Ju Hyeon; Lee, Joon-Seok; Sim, Jae Young; Seo, Jung Yoon; Oh, You-Kwan; Yang, Seung-Man; Kim, Shin-Hyun

2014-09-03

Photonic microdisks with a multilayered structure are designed from photocurable suspensions by step-by-step photolithography. In each step of photolithography, either a colloidal photonic crystal or a magnetic-particle-laden layer is stacked over the windows of a photomask. Sequential photolithography enables the creation of multilayered photonic microdisks that have brilliant structural colors that can be switched by an external magnetic field. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two-step sequential pretreatment for the enhanced enzymatic hydrolysis of coffee spent waste.

PubMed

Ravindran, Rajeev; Jaiswal, Swarna; Abu-Ghannam, Nissreen; Jaiswal, Amit K

2017-09-01

In the present study, eight different pretreatments of varying nature (physical, chemical and physico-chemical) followed by a sequential, combinatorial pretreatment strategy was applied to spent coffee waste to attain maximum sugar yield. Pretreated samples were analysed for total reducing sugar, individual sugars and generation of inhibitory compounds such as furfural and hydroxymethyl furfural (HMF) which can hinder microbial growth and enzyme activity. Native spent coffee waste was high in hemicellulose content. Galactose was found to be the predominant sugar in spent coffee waste. Results showed that sequential pretreatment yielded 350.12mg of reducing sugar/g of substrate, which was 1.7-fold higher than in native spent coffee waste (203.4mg/g of substrate). Furthermore, extensive delignification was achieved using sequential pretreatment strategy. XRD, FTIR, and DSC profiles of the pretreated substrates were studied to analyse the various changes incurred in sequentially pretreated spent coffee waste as opposed to native spent coffee waste. Copyright © 2017 Elsevier Ltd. All rights reserved.

General Methods for Analysis of Sequential “n-step” Kinetic Mechanisms: Application to Single Turnover Kinetics of Helicase-Catalyzed DNA Unwinding

PubMed Central

Lucius, Aaron L.; Maluf, Nasib K.; Fischer, Christopher J.; Lohman, Timothy M.

2003-01-01

Helicase-catalyzed DNA unwinding is often studied using “all or none” assays that detect only the final product of fully unwound DNA. Even using these assays, quantitative analysis of DNA unwinding time courses for DNA duplexes of different lengths, L, using “n-step” sequential mechanisms, can reveal information about the number of intermediates in the unwinding reaction and the “kinetic step size”, m, defined as the average number of basepairs unwound between two successive rate limiting steps in the unwinding cycle. Simultaneous nonlinear least-squares analysis using “n-step” sequential mechanisms has previously been limited by an inability to float the number of “unwinding steps”, n, and m, in the fitting algorithm. Here we discuss the behavior of single turnover DNA unwinding time courses and describe novel methods for nonlinear least-squares analysis that overcome these problems. Analytic expressions for the time courses, fss(t), when obtainable, can be written using gamma and incomplete gamma functions. When analytic expressions are not obtainable, the numerical solution of the inverse Laplace transform can be used to obtain fss(t). Both methods allow n and m to be continuous fitting parameters. These approaches are generally applicable to enzymes that translocate along a lattice or require repetition of a series of steps before product formation. PMID:14507688

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir

PubMed Central

Montaner, Luis J.

2017-01-01

Abstract Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects. We focus on strategies that may maximize target recognition and eradication by the sequential activation of a reconstituted immune system, together with delivery of optimal T-cell responses that can eliminate the reservoir and serve as means to maintain control of HIV spread in the absence of antiretroviral therapy (ART). As evidenced by the evolution of ART, we argue that a combination of immune-based strategies will be a superior path to cell-mediated HIV control and eradication. Available data from several human pilot trials already identify target strategies that may maximize antiviral pressure by joining innate and engineered T cell responses toward testing for sustained HIV remission and/or cure. PMID:28520969

Cultivating secondary traumatic growth among healthcare workers: the role of social support and self-efficacy.

PubMed

Shoji, Kotaro; Bock, Judith; Cieslak, Roman; Zukowska, Katarzyna; Luszczynska, Aleksandra; Benight, Charles C

2014-09-01

This 2-study longitudinal investigation examined the indirect effects of secondary traumatic stress (STS) on secondary traumatic growth via two mediators: perceived social support and secondary trauma self-efficacy. In particular, we tested if the 2 hypothetical mediators operate sequentially, that is, with secondary trauma self-efficacy facilitating social support (i.e., cultivation hypothesis) and/or social support enhancing self-efficacy (i.e., enabling hypothesis). Participants in Study 1 (N = 293 at Time 1, N = 115 at Time 2) were behavioral healthcare providers working with U.S. military personnel suffering from trauma. Study 2 was conducted among Polish healthcare workers (N = 298 at Time 1, N = 189 at Time 2) providing services for civilian survivors of traumatic events. In both studies, multiple mediational analyses showed evidence for the cultivation hypothesis. The relationship between STS at Time 1 and secondary traumatic growth at Time 2 was mediated sequentially by secondary trauma self-efficacy at Time 1 and social support at Time 2. The enabling hypothesis was not supported. Education and development programs for healthcare workers may benefit from boosting self-efficacy with the intent to facilitate perceived social support. © 2014 Wiley Periodicals, Inc.

Biohydrogen and methane production via a two-step process using an acid pretreated native microalgae consortium.

PubMed

Carrillo-Reyes, Julian; Buitrón, Germán

2016-12-01

A native microalgae consortium treated under thermal-acidic hydrolysis was used to produce hydrogen and methane in a two-step sequential process. Different acid concentrations were tested, generating hydrogen and methane yields of up to 45mLH 2 gVS -1 and 432mLCH 4 gVS -1 , respectively. The hydrogen production step solubilized the particulate COD (chemical oxygen demand) up to 30%, creating considerable amounts of volatile fatty acids (up to 10gCODL -1 ). It was observed that lower acid concentration presented higher hydrogen and methane production potential. The results revealed that thermal acid hydrolysis of a native microalgae consortium is a simple but effective strategy for producing hydrogen and methane in the sequential process. In addition to COD removal (50-70%), this method resulted in an energy recovery of up to 15.9kJ per g of volatile solids of microalgae biomass, one of the highest reported. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomimicry Promotes the Efficiency of a 10-Step Sequential Enzymatic Reaction on Nanoparticles, Converting Glucose to Lactate.

PubMed

Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L; Lata, James P; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M; Bergkvist, Magnus; Sherwood, Robert W; Zhang, Sheng; Travis, Alexander J

2017-01-02

For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biomimicry promotes the efficiency of a 10-step sequential enzymatic reaction on nanoparticles, converting glucose to lactate

PubMed Central

Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L.; Lata, James P.; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M.; Bergkvist, Magnus; Sherwood, Robert W.; Zhang, Sheng; Travis, Alexander J.

2016-01-01

For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. PMID:27901298

Multiple interactions drive adaptor-mediated recruitment of the ubiquitin ligase rsp5 to membrane proteins in vivo and in vitro.

PubMed

Sullivan, James A; Lewis, Michael J; Nikko, Elina; Pelham, Hugh R B

2007-07-01

Recognition of membrane proteins by the Nedd4/Rsp5 ubiquitin ligase family is a critical step in their targeting to the multivesicular body pathway. Some substrates contain "PY" motifs (PPxY), which bind to WW domains in the ligase. Others lack PY motifs and instead rely on adaptors that recruit the ligase to them. To investigate the mechanism of adaptor-mediated ubiquitination, we have characterized the interactions between the adaptor Bsd2, the ubiquitin ligase Rsp5, and the membrane proteins Cps1, Tre1, and Smf1 from Saccharomyces cerevisiae. We have reconstituted adaptor-mediated modification of Cps1 and Tre1 in vitro, and we show that two PY motifs in Bsd2 and two WW domains (WW2 and WW3) in Rsp5 are crucial for this. The binding of a weak noncanonical DMAPSY motif in Bsd2 to WW3 is an absolute requirement for Bsd2 adaptor function. We show that sorting of the manganese transporter Smf1, which requires both Bsd2 and Tre1, depends upon two PY motifs in Bsd2 and one motif in Tre1 but only two WW domains in Rsp5. We suggest that sequential assembly of first a Bsd2/Rsp5 complex, then a Tre1/Bsd2/Rsp5 complex followed by a rearrangement of PY-WW interactions is required for the ubiquitination of Smf1.

Multiple Interactions Drive Adaptor-Mediated Recruitment of the Ubiquitin Ligase Rsp5 to Membrane Proteins In Vivo and In Vitro

PubMed Central

Sullivan, James A.; Lewis, Michael J.; Nikko, Elina

2007-01-01

Recognition of membrane proteins by the Nedd4/Rsp5 ubiquitin ligase family is a critical step in their targeting to the multivesicular body pathway. Some substrates contain “PY” motifs (PPxY), which bind to WW domains in the ligase. Others lack PY motifs and instead rely on adaptors that recruit the ligase to them. To investigate the mechanism of adaptor-mediated ubiquitination, we have characterized the interactions between the adaptor Bsd2, the ubiquitin ligase Rsp5, and the membrane proteins Cps1, Tre1, and Smf1 from Saccharomyces cerevisiae. We have reconstituted adaptor-mediated modification of Cps1 and Tre1 in vitro, and we show that two PY motifs in Bsd2 and two WW domains (WW2 and WW3) in Rsp5 are crucial for this. The binding of a weak noncanonical DMAPSY motif in Bsd2 to WW3 is an absolute requirement for Bsd2 adaptor function. We show that sorting of the manganese transporter Smf1, which requires both Bsd2 and Tre1, depends upon two PY motifs in Bsd2 and one motif in Tre1 but only two WW domains in Rsp5. We suggest that sequential assembly of first a Bsd2/Rsp5 complex, then a Tre1/Bsd2/Rsp5 complex followed by a rearrangement of PY–WW interactions is required for the ubiquitination of Smf1. PMID:17429078

Sequential control of step-bunching during graphene growth on SiC (0001)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bao, Jianfeng; Kusunoki, Michiko; Yasui, Osamu

2016-08-22

We have investigated the relation between the step-bunching and graphene growth phenomena on an SiC substrate. We found that only a minimum amount of step-bunching occurred during the graphene growth process with a high heating rate. On the other hand, a large amount of step-bunching occurred using a slow heating process. These results indicated that we can control the degree of step-bunching during graphene growth by controlling the heating rate. We also found that graphene coverage suppressed step bunching, which is an effective methodology not only in the graphene technology but also in the SiC-based power electronics.

Dynamics of Sequential Decision Making

NASA Astrophysics Data System (ADS)

Rabinovich, Mikhail I.; Huerta, Ramón; Afraimovich, Valentin

2006-11-01

We suggest a new paradigm for intelligent decision-making suitable for dynamical sequential activity of animals or artificial autonomous devices that depends on the characteristics of the internal and external world. To do it we introduce a new class of dynamical models that are described by ordinary differential equations with a finite number of possibilities at the decision points, and also include rules solving this uncertainty. Our approach is based on the competition between possible cognitive states using their stable transient dynamics. The model controls the order of choosing successive steps of a sequential activity according to the environment and decision-making criteria. Two strategies (high-risk and risk-aversion conditions) that move the system out of an erratic environment are analyzed.

The Relationship Between Education and Prostate-Specific Antigen Testing Among Urban African American Medicare Beneficiaries

PubMed Central

Pollack, Craig Evan; Garza, Mary A.; Yeh, Hsin-Chieh; Markakis, Diane; Phelan-Emrick, Darcy F.; Wenzel, Jennifer; Shapiro, Gary R.; Bone, Lee; Johnson, Lawrence

2017-01-01

Purpose We examined the association between socioeconomic status (SES) and prostate-specific antigen (PSA) cancer screening among older African American men. Methods We analyzed baseline data from a sample of 485 community-dwelling African American men who participated in the Cancer Prevention and Treatment Demonstration Trial. The outcome was receipt of PSA screening within the past year. SES was measured using income and educational attainment. Sequential multivariate logistic regression models were performed to study whether health care access, patient–provider relationship, and cancer fatalism mediated the relationship between SES and PSA screening. Results Higher educational attainment was significantly associated with higher odds of PSA screening in the past year (odds ratio (OR) 2.08 for college graduate compared to less than high school graduate, 95 % confidence interval (CI) 1.03–4.24); income was not. Health care access and patient–provider communication did not alter the relationship between education and screening; however, beliefs regarding cancer fatalism partially mediated the observed relationship. Conclusion Rates of prostate cancer screening among African American men vary by level of educational attainment; beliefs concerning cancer fatalism help explain this gradient. Understanding the determinants of cancer fatalism is a critical next step in building interventions that seek to ensure equitable access to prostate cancer screening. PMID:26863336

The Relationship Between Education and Prostate-Specific Antigen Testing Among Urban African American Medicare Beneficiaries.

PubMed

Hararah, Mohammad Khalid; Pollack, Craig Evan; Garza, Mary A; Yeh, Hsin-Chieh; Markakis, Diane; Phelan-Emrick, Darcy F; Wenzel, Jennifer; Shapiro, Gary R; Bone, Lee; Johnson, Lawrence; Ford, Jean G

2015-06-01

We examined the association between socioeconomic status (SES) and prostate-specific antigen (PSA) cancer screening among older African American men. We analyzed baseline data from a sample of 485 community-dwelling African American men who participated in the Cancer Prevention and Treatment Demonstration Trial. The outcome was receipt of PSA screening within the past year. SES was measured using income and educational attainment. Sequential multivariate logistic regression models were performed to study whether health care access, patient-provider relationship, and cancer fatalism mediated the relationship between SES and PSA screening. Higher educational attainment was significantly associated with higher odds of PSA screening in the past year (odds ratio (OR) 2.08 for college graduate compared to less than high school graduate, 95 % confidence interval (CI) 1.03-4.24); income was not. Health care access and patient-provider communication did not alter the relationship between education and screening; however, beliefs regarding cancer fatalism partially mediated the observed relationship. Rates of prostate cancer screening among African American men vary by level of educational attainment; beliefs concerning cancer fatalism help explain this gradient. Understanding the determinants of cancer fatalism is a critical next step in building interventions that seek to ensure equitable access to prostate cancer screening.

Two-step estimation in ratio-of-mediator-probability weighted causal mediation analysis.

PubMed

Bein, Edward; Deutsch, Jonah; Hong, Guanglei; Porter, Kristin E; Qin, Xu; Yang, Cheng

2018-04-15

This study investigates appropriate estimation of estimator variability in the context of causal mediation analysis that employs propensity score-based weighting. Such an analysis decomposes the total effect of a treatment on the outcome into an indirect effect transmitted through a focal mediator and a direct effect bypassing the mediator. Ratio-of-mediator-probability weighting estimates these causal effects by adjusting for the confounding impact of a large number of pretreatment covariates through propensity score-based weighting. In step 1, a propensity score model is estimated. In step 2, the causal effects of interest are estimated using weights derived from the prior step's regression coefficient estimates. Statistical inferences obtained from this 2-step estimation procedure are potentially problematic if the estimated standard errors of the causal effect estimates do not reflect the sampling uncertainty in the estimation of the weights. This study extends to ratio-of-mediator-probability weighting analysis a solution to the 2-step estimation problem by stacking the score functions from both steps. We derive the asymptotic variance-covariance matrix for the indirect effect and direct effect 2-step estimators, provide simulation results, and illustrate with an application study. Our simulation results indicate that the sampling uncertainty in the estimated weights should not be ignored. The standard error estimation using the stacking procedure offers a viable alternative to bootstrap standard error estimation. We discuss broad implications of this approach for causal analysis involving propensity score-based weighting. Copyright © 2018 John Wiley & Sons, Ltd.

Humanizing Outgroups Through Multiple Categorization

PubMed Central

Prati, Francesca; Crisp, Richard J.; Meleady, Rose; Rubini, Monica

2016-01-01

In three studies, we examined the impact of multiple categorization on intergroup dehumanization. Study 1 showed that perceiving members of a rival university along multiple versus simple categorical dimensions enhanced the tendency to attribute human traits to this group. Study 2 showed that multiple versus simple categorization of immigrants increased the attribution of uniquely human emotions to them. This effect was explained by the sequential mediation of increased individuation of the outgroup and reduced outgroup threat. Study 3 replicated this sequential mediation model and introduced a novel way of measuring humanization in which participants generated attributes corresponding to the outgroup in a free response format. Participants generated more uniquely human traits in the multiple versus simple categorization conditions. We discuss the theoretical implications of these findings and consider their role in informing and improving efforts to ameliorate contemporary forms of intergroup discrimination. PMID:26984016

Biogenesis of the Saccharomyces cerevisiae Pheromone a-Factor, from Yeast Mating to Human Disease

PubMed Central

Barrowman, Jemima

2012-01-01

Summary: The mating pheromone a-factor secreted by Saccharomyces cerevisiae is a farnesylated and carboxylmethylated peptide and is unusually hydrophobic compared to other extracellular signaling molecules. Mature a-factor is derived from a precursor with a C-terminal CAAX motif that directs a series of posttranslational reactions, including prenylation, endoproteolysis, and carboxylmethylation. Historically, a-factor has served as a valuable model for the discovery and functional analysis of CAAX-processing enzymes. In this review, we discuss the three modules comprising the a-factor biogenesis pathway: (i) the C-terminal CAAX-processing steps carried out by Ram1/Ram2, Ste24 or Rce1, and Ste14; (ii) two sequential N-terminal cleavage steps, mediated by Ste24 and Axl1; and (iii) export by a nonclassical mechanism, mediated by the ATP binding cassette (ABC) transporter Ste6. The small size and hydrophobicity of a-factor present both challenges and advantages for biochemical analysis, as discussed here. The enzymes involved in a-factor biogenesis are conserved from yeasts to mammals. Notably, studies of the zinc metalloprotease Ste24 in S. cerevisiae led to the discovery of its mammalian homolog ZMPSTE24, which cleaves the prenylated C-terminal tail of the nuclear scaffold protein lamin A. Mutations that alter ZMPSTE24 processing of lamin A in humans cause the premature-aging disease progeria and related progeroid disorders. Intriguingly, recent evidence suggests that the entire a-factor pathway, including all three biogenesis modules, may be used to produce a prenylated, secreted signaling molecule involved in germ cell migration in Drosophila. Thus, additional prenylated signaling molecules resembling a-factor, with as-yet-unknown roles in metazoan biology, may await discovery. PMID:22933563

A Bayesian sequential design using alpha spending function to control type I error.

PubMed

Zhu, Han; Yu, Qingzhao

2017-10-01

We propose in this article a Bayesian sequential design using alpha spending functions to control the overall type I error in phase III clinical trials. We provide algorithms to calculate critical values, power, and sample sizes for the proposed design. Sensitivity analysis is implemented to check the effects from different prior distributions, and conservative priors are recommended. We compare the power and actual sample sizes of the proposed Bayesian sequential design with different alpha spending functions through simulations. We also compare the power of the proposed method with frequentist sequential design using the same alpha spending function. Simulations show that, at the same sample size, the proposed method provides larger power than the corresponding frequentist sequential design. It also has larger power than traditional Bayesian sequential design which sets equal critical values for all interim analyses. When compared with other alpha spending functions, O'Brien-Fleming alpha spending function has the largest power and is the most conservative in terms that at the same sample size, the null hypothesis is the least likely to be rejected at early stage of clinical trials. And finally, we show that adding a step of stop for futility in the Bayesian sequential design can reduce the overall type I error and reduce the actual sample sizes.

Coordination of two sequential ester-transfer reactions: exogenous guanosine binding promotes the subsequent ωG binding to a group I intron

PubMed Central

Bao, Penghui; Wu, Qi-Jia; Yin, Ping; Jiang, Yanfei; Wang, Xu; Xie, Mao-Hua; Sun, Tao; Huang, Lin; Mo, Ding-Ding; Zhang, Yi

2008-01-01

Self-splicing of group I introns is accomplished by two sequential ester-transfer reactions mediated by sequential binding of two different guanosine ligands, but it is yet unclear how the binding is coordinated at a single G-binding site. Using a three-piece trans-splicing system derived from the Candida intron, we studied the effect of the prior GTP binding on the later ωG binding by assaying the ribozyme activity in the second reaction. We showed that adding GTP simultaneously with and prior to the esterified ωG in a substrate strongly accelerated the second reaction, suggesting that the early binding of GTP facilitates the subsequent binding of ωG. GTP-mediated facilitation requires C2 amino and C6 carbonyl groups on the Watson–Crick edge of the base but not the phosphate or sugar groups, suggesting that the base triple interactions between GTP and the binding site are important for the subsequent ωG binding. Strikingly, GTP binding loosens a few local structures of the ribozyme including that adjacent to the base triple, providing structural basis for a rapid exchange of ωG for bound GTP. PMID:18978026

Rise and fall of political complexity in island South-East Asia and the Pacific.

PubMed

Currie, Thomas E; Greenhill, Simon J; Gray, Russell D; Hasegawa, Toshikazu; Mace, Ruth

2010-10-14

There is disagreement about whether human political evolution has proceeded through a sequence of incremental increases in complexity, or whether larger, non-sequential increases have occurred. The extent to which societies have decreased in complexity is also unclear. These debates have continued largely in the absence of rigorous, quantitative tests. We evaluated six competing models of political evolution in Austronesian-speaking societies using phylogenetic methods. Here we show that in the best-fitting model political complexity rises and falls in a sequence of small steps. This is closely followed by another model in which increases are sequential but decreases can be either sequential or in bigger drops. The results indicate that large, non-sequential jumps in political complexity have not occurred during the evolutionary history of these societies. This suggests that, despite the numerous contingent pathways of human history, there are regularities in cultural evolution that can be detected using computational phylogenetic methods.

Removal of ion-implanted photoresists on GaAs using two organic solvents in sequence

NASA Astrophysics Data System (ADS)

Oh, Eunseok; Na, Jihoon; Lee, Seunghyo; Lim, Sangwoo

2016-07-01

Organic solvents can effectively remove photoresists on III-V channels without damage or etching of the channel material during the process. In this study, a two-step sequential photoresist removal process using two different organic solvents was developed to remove implanted ArF and KrF photoresists at room temperature. The effects of organic solvents with either low molar volumes or high affinities for photoresists were evaluated to find a proper combination that can effectively remove high-dose implanted photoresists without damaging GaAs surfaces. The performance of formamide, acetonitrile, nitromethane, and monoethanolamine for the removal of ion-implanted ArF and KrF photoresists were compared using a two-step sequential photoresist removal process followed by treatment in dimethyl sulfoxide (DMSO). Among the various combinations, the acetonitrile + DMSO two-step sequence exhibited the best removal of photoresists that underwent ion implantation at doses of 5 × 1013-5 × 1015 atoms/cm2 on both flat and trench-structured GaAs surfaces. The ability of the two-step process using organic solvents to remove the photoresists can be explained by considering the affinities of solvents for a polymer and its permeability through the photoresist.

Comparison of two commercial embryo culture media (SAGE-1 step single medium vs. G1-PLUSTM/G2-PLUSTM sequential media): Influence on in vitro fertilization outcomes and human embryo quality.

PubMed

López-Pelayo, Iratxe; Gutiérrez-Romero, Javier María; Armada, Ana Isabel Mangano; Calero-Ruiz, María Mercedes; Acevedo-Yagüe, Pablo Javier Moreno de

2018-04-26

To compare embryo quality, fertilization, implantation, miscarriage and clinical pregnancy rates for embryos cultured in two different commercial culture media until D-2 or D-3. In this retrospective study, we analyzed 189 cycles performed in 2016. Metaphase II oocytes were microinjected and allocated into single medium (SAGE 1-STEP, Origio) until transferred, frozen or discarded; or, if sequential media were used, the oocytes were cultured in G1-PLUSTM (Vitrolife) up to D-2 or D-3 and in G2-PLUSTM (Vitrolife) to transfer. On the following day, the oocytes were checked for normal fertilization and on D-2 and D-3 for morphological classification. Statistical analysis was performed using the chi-square and Mann-Whitney tests in PASW Statistics 18.0. The fertilization rates were 70.07% for single and 69.11% for sequential media (p=0.736). The mean number of embryos with high morphological quality (class A/B) was higher in the single medium than in the sequential media: D-2 [class A (190 vs. 107, p<0.001), B (133 vs. 118, p=0.018)]; D-3 [class A (40 vs. 19, p=0.048) but without differences in class B (40 vs. 49)]. Consequently, a higher number of embryos cultured in single medium were frozen: 197 (21.00%) vs. sequential: 102 (11.00%), p<0.001. No differences were found in implantation rates (30.16% vs. 25.57%, p=0.520), clinical pregnancy rates (55.88% vs. 41.05%, p=0.213), or miscarriage rates (14.29% vs. 9.52%, p=0.472). Embryo culture in single medium yields greater efficiency per cycle than in sequential media. Higher embryo quality and quantity were achieved, resulting in more frozen embryos. There were no differences in clinical pregnancy rates.

The Obstacles for the Teaching of 8th Grade TR History of Revolution and Kemalism Course According to the Constructivist Approach (An Example of Exploratory Sequential Mixed Method Design)

ERIC Educational Resources Information Center

Karademir, Yavuz; Demir, Selcuk Besir

2015-01-01

The aim of this study is to ascertain the problems social studies teachers face in the teaching of topics covered in 8th grade TRHRK Course. The study was conducted in line with explanatory sequential mixed method design, which is one of the mixed research method, was used. The study involves three phases. In the first step, exploratory process…

Enantioselective synthesis of syn/anti-1,3-amino alcohols via proline-catalyzed sequential alpha-aminoxylation/alpha-amination and Horner-Wadsworth-Emmons olefination of aldehydes.

PubMed

Jha, Vishwajeet; Kondekar, Nagendra B; Kumar, Pradeep

2010-06-18

A novel and general method for asymmetric synthesis of both syn/anti-1,3-amino alcohols is described. The method uses proline-catalyzed sequential alpha-aminoxylation/ alpha-amination and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes as the key step. By using this method, a short synthesis of a bioactive molecule, (R)-1-((S)-1-methylpyrrolidin-2-yl)-5-phenylpentan-2-ol, is also accomplished.

Pollution potential leaching index as a tool to assess water leaching risk of arsenic in excavated urban soils.

PubMed

Li, Jining; Kosugi, Tomoya; Riya, Shohei; Hashimoto, Yohey; Hou, Hong; Terada, Akihiko; Hosomi, Masaaki

2018-01-01

Leaching of hazardous trace elements from excavated urban soils during construction of cities has received considerable attention in recent years in Japan. A new concept, the pollution potential leaching index (PPLI), was applied to assess the risk of arsenic (As) leaching from excavated soils. Sequential leaching tests (SLT) with two liquid-to-solid (L/S) ratios (10 and 20Lkg -1 ) were conducted to determine the PPLI values, which represent the critical cumulative L/S ratios at which the average As concentrations in the cumulative leachates are reduced to critical values (10 or 5µgL -1 ). Two models (a logarithmic function model and an empirical two-site first-order leaching model) were compared to estimate the PPLI values. The fractionations of As before and after SLT were extracted according to a five-step sequential extraction procedure. Ten alkaline excavated soils were obtained from different construction projects in Japan. Although their total As contents were low (from 6.75 to 79.4mgkg -1 ), the As leaching was not negligible. Different L/S ratios at each step of the SLT had little influence on the cumulative As release or PPLI values. Experimentally determined PPLI values were in agreement with those from model estimations. A five-step SLT with an L/S of 10Lkg -1 at each step, combined with a logarithmic function fitting was suggested for the easy estimation of PPLI. Results of the sequential extraction procedure showed that large portions of more labile As fractions (non-specifically and specifically sorbed fractions) were removed during long-term leaching and so were small, but non-negligible, portions of strongly bound As fractions. Copyright © 2017 Elsevier Inc. All rights reserved.

Unraveling the B. pseudomallei Heptokinase WcbL: From Structure to Drug Discovery

PubMed Central

Vivoli, Mirella; Isupov, Michail N.; Nicholas, Rebecca; Hill, Andrew; Scott, Andrew E.; Kosma, Paul; Prior, Joann L.; Harmer, Nicholas J.

2015-01-01

Summary Gram-negative bacteria utilize heptoses as part of their repertoire of extracellular polysaccharide virulence determinants. Disruption of heptose biosynthesis offers an attractive target for novel antimicrobials. A critical step in the synthesis of heptoses is their 1-O phosphorylation, mediated by kinases such as HldE or WcbL. Here, we present the structure of WcbL from Burkholderia pseudomallei. We report that WcbL operates through a sequential ordered Bi-Bi mechanism, loading the heptose first and then ATP. We show that dimeric WcbL binds ATP anti-cooperatively in the absence of heptose, and cooperatively in its presence. Modeling of WcbL suggests that heptose binding causes an elegant switch in the hydrogen-bonding network, facilitating the binding of a second ATP molecule. Finally, we screened a library of drug-like fragments, identifying hits that potently inhibit WcbL. Our results provide a novel mechanism for control of substrate binding and emphasize WcbL as an attractive anti-microbial target for Gram-negative bacteria. PMID:26687481

Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens.

PubMed

Tatsis, Nia; Lasaro, Marcio O; Lin, Shih-Wen; Haut, Larissa H; Xiang, Zhi Q; Zhou, Dongming; Dimenna, Lauren; Li, Hua; Bian, Ang; Abdulla, Sarah; Li, Yan; Giles-Davis, Wynetta; Engram, Jessica; Ratcliffe, Sarah J; Silvestri, Guido; Ertl, Hildegund C; Betts, Michael R

2009-05-15

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.

Unexpected regioselective carbon-hydrogen bond activation/cyclization of indolyl aldehydes or ketones with alkynes to benzo-fused oxindoles.

PubMed

Liu, Xingyan; Li, Gaocan; Song, Feijie; You, Jingsong

2014-09-25

Rhodium-catalyzed carbon-hydrogen bond activation has attracted great interest in the construction of carbon-carbon and carbon-heteroatom bonds. In recent years, transition metal-mediated oxygen transposition through a 'dehydration-rehydration' process has been considered as a promising strategy towards oxygen-functionalized compounds. Here we describe an unexpected rhodium-catalyzed regioselective carbon-hydrogen bond activation/cyclization of easily available indolyl aldehydes or ketones with alkynes to afford benzo-fused oxindoles, involving the sequential carbonyl-assisted carbon-hydrogen activation of the indole ring at the 4-position, [4+2] cyclization, aromatization via dehydration, nucleophilic addition of water to iminium and oxidation. Isotopic labelling experiments disclose the occurrence of apparent oxygen transposition via dehydration-rehydration from the indolyl-3-carbonyl group to the 2-position of pyrrole to forge a new carbonyl bond. The tandem reaction has been used as the key step for the concise synthesis of priolines, a type of alkaloid isolated from the roots of Salvia prionitis.

Relative judgment theory and the mediation of facial recognition: Implications for theories of eyewitness identification.

PubMed

McAdoo, Ryan M; Gronlund, Scott D

2016-01-01

Many in the eyewitness identification community believe that sequential lineups are superior to simultaneous lineups because simultaneous lineups encourage inappropriate choosing due to promoting comparisons among choices (a relative judgment strategy), but sequential lineups reduce this propensity by inducing comparisons of lineup members directly to memory rather than to each other (an absolute judgment strategy). Different versions of the relative judgment theory have implicated both discrete-state and continuous mediation of eyewitness decisions. The theory has never been formally specified, but (Yonelinas, J Exp Psychol Learn Mem Cogn 20:1341-1354, 1994) dual-process models provide one possible specification, thereby allowing us to evaluate how eyewitness decisions are mediated. We utilized a ranking task (Kellen and Klauer, J Exp Psychol Learn Mem Cogn 40:1795-1804, 2014) and found evidence for continuous mediation when facial stimuli match from study to test (Experiment 1) and when they mismatch (Experiment 2). This evidence, which is contrary to a version of relative judgment theory that has gained a lot of traction in the legal community, compels reassessment of the role that guessing plays in eyewitness identification. Future research should continue to test formal explanations in order to advance theory, expedite the development of new procedures that can enhance the reliability of eyewitness evidence, and to facilitate the exploration of task factors and emergent strategies that might influence when recognition is continuously or discretely mediated.

Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM)-mediated Inhibitory Signaling is Regulated by Sequential Phosphorylation Mediated by Distinct Nonreceptor Tyrosine Kinases: A Case Study Involving PECAM-1

PubMed Central

Tourdot, Benjamin E.; Brenner, Michelle K.; Keough, Kathleen C.; Holyst, Trudy; Newman, Peter J.; Newman, Debra K.

2013-01-01

The activation state of many blood and vascular cells is tightly controlled by a delicate balance between receptors that contain immunoreceptor tyrosine-based activation motifs (ITAMs) and those that contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Precisely how the timing of cellular activation by ITAM-coupled receptors is regulated by ITIM-containing receptors is, however, poorly understood. Using platelet endothelial cell adhesion molecule 1 (PECAM-1) as a prototypical ITIM-bearing receptor, we demonstrate that initiation of inhibitory signaling occurs via a novel, sequential process in which Src family kinases phosphorylate the C-terminal ITIM, thereby enabling phosphorylation of the N-terminal ITIM of PECAM-1 by other Src homology 2 domain-containing non-receptor tyrosine kinases (NRTKs). NRTKs capable of mediating the second phosphorylation event include C-terminal Src kinase (Csk) and Bruton’s tyrosine kinase (Btk). Btk and Csk function downstream of phosphatidylinositol 3-kinase (PI3K) activation during ITAM-dependent platelet activation. In ITAM-activated platelets that were treated with a PI3K inhibitor, PECAM-1 was phosphorylated but did not bind the tandem SH2 domain-containing tyrosine phosphatase SHP-2, indicating that it was not phosphorylated on its N-terminal ITIM. Csk bound to and phosphorylated PECAM-1 more efficiently than did Btk, and required its SH2 domain to perform these functions. Additionally, the phosphorylation of the N-terminal ITIM of Siglec-9 by Csk is enhanced by the prior phosphorylation of its C-terminal ITIM, providing evidence that the ITIMs of other dual ITIM-containing receptors are also sequentially phosphorylated. On the basis of these findings, we propose that sequential ITIM phosphorylation provides a general mechanism for precise temporal control over the recruitment and activation of tandem SH2 domain-containing tyrosine phosphatases that dampen ITAM-dependent signals. PMID:23418871

An efficient sequential approach to tracking multiple objects through crowds for real-time intelligent CCTV systems.

PubMed

Li, Liyuan; Huang, Weimin; Gu, Irene Yu-Hua; Luo, Ruijiang; Tian, Qi

2008-10-01

Efficiency and robustness are the two most important issues for multiobject tracking algorithms in real-time intelligent video surveillance systems. We propose a novel 2.5-D approach to real-time multiobject tracking in crowds, which is formulated as a maximum a posteriori estimation problem and is approximated through an assignment step and a location step. Observing that the occluding object is usually less affected by the occluded objects, sequential solutions for the assignment and the location are derived. A novel dominant color histogram (DCH) is proposed as an efficient object model. The DCH can be regarded as a generalized color histogram, where dominant colors are selected based on a given distance measure. Comparing with conventional color histograms, the DCH only requires a few color components (31 on average). Furthermore, our theoretical analysis and evaluation on real data have shown that DCHs are robust to illumination changes. Using the DCH, efficient implementations of sequential solutions for the assignment and location steps are proposed. The assignment step includes the estimation of the depth order for the objects in a dispersing group, one-by-one assignment, and feature exclusion from the group representation. The location step includes the depth-order estimation for the objects in a new group, the two-phase mean-shift location, and the exclusion of tracked objects from the new position in the group. Multiobject tracking results and evaluation from public data sets are presented. Experiments on image sequences captured from crowded public environments have shown good tracking results, where about 90% of the objects have been successfully tracked with the correct identification numbers by the proposed method. Our results and evaluation have indicated that the method is efficient and robust for tracking multiple objects (>or= 3) in complex occlusion for real-world surveillance scenarios.

Hydrogels with Spatially and Temporally Controlled Properties to Control Cellular Interactions

NASA Astrophysics Data System (ADS)

Burdick, Jason

2011-03-01

Stem cells (e.g., mesenchymal stem cells, MSCs) respond to many cues from their microenvironment, which may include chemical signals, mechanics, and topography. Importantly, these cues may be incorporated into scaffolding to control stem cell differentiation and optimize their ability to produce tissues in regenerative medicine. Despite the significant amount of work in this area, the materials have been primarily static and uniform. To this end, we have developed a sequential crosslinking process that relies on our ability to crosslinked functional biopolymers (e.g., methacrylated hyaluronic acid, HA) in two steps, namely a Michael-type addition reaction to partially consume reactive groups and then a light-initiated free-radical polymerization to further crosslink the material. With light exposure during the second step comes control over the material in space (via masks and lasers) and time (via intermittent light exposure). We are applying this technique for numerous applications. For example, when the HA hydrogels are crosslinked with MMP degradable peptides with thiol termini during the first step, a material that can be degraded by cells is obtained. However, cell-mediated degradation is obstructed with the introduction of kinetic chains during the second step, leading to spatially controlled cell degradability. Due to the influence of cellular spreading on MSC differentiation, we have controlled cell fates by controlling their spread ability, for instance towards osteoblasts in spread areas and adipocytes when cell remained rounded. We are also using the process of stiffening with time to investigate mechanically induced differentiation, particularly in materials with evolving mechanics. Overall, these advanced HA hydrogels provide us the opportunity to investigate diverse and controlled material properties on MSC interactions.

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir.

PubMed

Riley, James L; Montaner, Luis J

2017-03-15

Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects. We focus on strategies that may maximize target recognition and eradication by the sequential activation of a reconstituted immune system, together with delivery of optimal T-cell responses that can eliminate the reservoir and serve as means to maintain control of HIV spread in the absence of antiretroviral therapy (ART). As evidenced by the evolution of ART, we argue that a combination of immune-based strategies will be a superior path to cell-mediated HIV control and eradication. Available data from several human pilot trials already identify target strategies that may maximize antiviral pressure by joining innate and engineered T cell responses toward testing for sustained HIV remission and/or cure. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

One-pot growth of two-dimensional lateral heterostructures via sequential edge-epitaxy

NASA Astrophysics Data System (ADS)

Sahoo, Prasana K.; Memaran, Shahriar; Xin, Yan; Balicas, Luis; Gutiérrez, Humberto R.

2018-01-01

Two-dimensional heterojunctions of transition-metal dichalcogenides have great potential for application in low-power, high-performance and flexible electro-optical devices, such as tunnelling transistors, light-emitting diodes, photodetectors and photovoltaic cells. Although complex heterostructures have been fabricated via the van der Waals stacking of different two-dimensional materials, the in situ fabrication of high-quality lateral heterostructures with multiple junctions remains a challenge. Transition-metal-dichalcogenide lateral heterostructures have been synthesized via single-step, two-step or multi-step growth processes. However, these methods lack the flexibility to control, in situ, the growth of individual domains. In situ synthesis of multi-junction lateral heterostructures does not require multiple exchanges of sources or reactors, a limitation in previous approaches as it exposes the edges to ambient contamination, compromises the homogeneity of domain size in periodic structures, and results in long processing times. Here we report a one-pot synthetic approach, using a single heterogeneous solid source, for the continuous fabrication of lateral multi-junction heterostructures consisting of monolayers of transition-metal dichalcogenides. The sequential formation of heterojunctions is achieved solely by changing the composition of the reactive gas environment in the presence of water vapour. This enables selective control of the water-induced oxidation and volatilization of each transition-metal precursor, as well as its nucleation on the substrate, leading to sequential edge-epitaxy of distinct transition-metal dichalcogenides. Photoluminescence maps confirm the sequential spatial modulation of the bandgap, and atomic-resolution images reveal defect-free lateral connectivity between the different transition-metal-dichalcogenide domains within a single crystal structure. Electrical transport measurements revealed diode-like responses across the junctions. Our new approach offers greater flexibility and control than previous methods for continuous growth of transition-metal-dichalcogenide-based multi-junction lateral heterostructures. These findings could be extended to other families of two-dimensional materials, and establish a foundation for the development of complex and atomically thin in-plane superlattices, devices and integrated circuits.

Acute Oral Toxicity Up-And-Down-Procedure

EPA Pesticide Factsheets

The Up-and-Down Procedure is an alternative acute toxicity test that provides a way to determine the toxicity of chemicals with fewer test animals by using sequential dosing steps. Find out about this test procedure.

Shipboard communications center modernization recommendations report

DOT National Transportation Integrated Search

1995-08-01

This report presents the results of a communications system modernization study for the radio room of the U.S. Coast Guard (USCG) high endurance cutter (WHEC) and medium endurance cutter (WMEC). A four step sequential analysis approach was undertaken...

Membrane augmented distillation to separate solvents from water

DOEpatents

Huang, Yu; Baker, Richard W.; Daniels, Rami; Aldajani, Tiem; Ly, Jennifer H.; Alvarez, Franklin R.; Vane, Leland M.

2012-09-11

Processes for removing water from organic solvents, such as ethanol. The processes include distillation to form a rectified overhead vapor, compression of the rectified vapor, and treatment of the compressed vapor by two sequential membrane separation steps.

Trip generation characteristics of special generators

DOT National Transportation Integrated Search

2010-03-01

Special generators are introduced in the sequential four-step modeling procedure to represent certain types of facilities whose trip generation characteristics are not fully captured by the standard trip generation module. They are also used in the t...

Positive feedback : exploring current approaches in iterative travel demand model implementation.

DOT National Transportation Integrated Search

2012-01-01

Currently, the models that TxDOTs Transportation Planning and Programming Division (TPP) developed are : traditional three-step models (i.e., trip generation, trip distribution, and traffic assignment) that are sequentially : applied. A limitation...

Article and method for making an article

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lacy, Benjamin Paul; Schick, David Edward; Kottilingam, Srikanth Chandrudu

An article and a method for making shaped cooling holes in an article are provided. The method includes the steps of depositing a metal alloy powder to form an initial layer including at least one aperture, melting the metal alloy powder with a focused energy source to transform the powder layer to a sheet of metal alloy, sequentially depositing an additional layer of the metal alloy powder to form a layer including at least one aperture corresponding to the at least one aperture in the initial layer, melting the additional layer of the metal alloy powder with the focused energymore » source to increase the sheet thickness, and repeating the steps of sequentially depositing and melting the additional layers of metal alloy powder until a structure including at least one aperture having a predetermined profile is obtained. The structure is attached to a substrate to make the article.« less

Investigations of Cu, Pb and Zn partitioning by sequential extraction in harbour sediments after electrodialytic remediation.

PubMed

Kirkelund, Gunvor M; Ottosen, Lisbeth M; Villumsen, Arne

2010-05-01

Electrodialytic remediation was used to remove Cu, Zn and Pb from three different contaminated harbour sediments. Electrodialytic experiments lasting 2 and 4 weeks were performed and 48-86% Cu, 74-90% Zn and 62-88% Pb were removed from the different sediments and the removal increased with longer remediation time. A three step sequential extraction scheme (BCR), with an extra residual step, was used to evaluate the heavy metal distribution in the sediments before and after electrodialytic remediation. Cu was mainly associated with the oxidisable phase of the sediment, both before and after remediation. Zn and Pb were found in the exchangeable and reducible phases before remediation. Zn was still found in the exchangeable and reducible phases after remediation, whereas most Pb was removed from these phases during electrodialytic remediation. Copyright 2010 Elsevier Ltd. All rights reserved.

Regio- and Enantioselective Sequential Dehalogenation of rac-1,3-Dibromobutane by Haloalkane Dehalogenase LinB.

PubMed

Gross, Johannes; Prokop, Zbyněk; Janssen, Dick; Faber, Kurt; Hall, Mélanie

2016-08-03

The hydrolytic dehalogenation of rac-1,3-dibromobutane catalyzed by the haloalkane dehalogenase LinB from Sphingobium japonicum UT26 proceeds in a sequential fashion: initial formation of intermediate haloalcohols followed by a second hydrolytic step to produce the final diol. Detailed investigation of the course of the reaction revealed favored nucleophilic displacement of the sec-halogen in the first hydrolytic event with pronounced R enantioselectivity. The second hydrolysis step proceeded with a regioselectivity switch at the primary position, with preference for the S enantiomer. Because of complex competition between all eight possible reactions, intermediate haloalcohols formed with moderate to good ee ((S)-4-bromobutan-2-ol: up to 87 %). Similarly, (S)-butane-1,3-diol was formed at a maximum ee of 35 % before full hydrolysis furnished the racemic diol product. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strategic disruption of nuclear pores structure, integrity and barrier for nuclear apoptosis.

PubMed

Shahin, Victor

2017-08-01

Apoptosis is a programmed cell death playing key roles in physiology and pathophysiology of multi cellular organisms. Its nuclear manifestation requires transmission of the death signals across the nuclear pore complexes (NPCs). In strategic sequential steps apoptotic factors disrupt NPCs structure, integrity and barrier ultimately leading to nuclear breakdown. The present review reflects on these steps. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sequential (step-by-step) detection, identification and quantitation of extra virgin olive oil adulteration by chemometric treatment of chromatographic profiles.

PubMed

Capote, F Priego; Jiménez, J Ruiz; de Castro, M D Luque

2007-08-01

An analytical method for the sequential detection, identification and quantitation of extra virgin olive oil adulteration with four edible vegetable oils--sunflower, corn, peanut and coconut oils--is proposed. The only data required for this method are the results obtained from an analysis of the lipid fraction by gas chromatography-mass spectrometry. A total number of 566 samples (pure oils and samples of adulterated olive oil) were used to develop the chemometric models, which were designed to accomplish, step-by-step, the three aims of the method: to detect whether an olive oil sample is adulterated, to identify the type of adulterant used in the fraud, and to determine how much aldulterant is in the sample. Qualitative analysis was carried out via two chemometric approaches--soft independent modelling of class analogy (SIMCA) and K nearest neighbours (KNN)--both approaches exhibited prediction abilities that were always higher than 91% for adulterant detection and 88% for type of adulterant identification. Quantitative analysis was based on partial least squares regression (PLSR), which yielded R2 values of >0.90 for calibration and validation sets and thus made it possible to determine adulteration with excellent precision according to the Shenk criteria.

Three parameters optimizing closed-loop control in sequential segmental neuromuscular stimulation.

PubMed

Zonnevijlle, E D; Somia, N N; Perez Abadia, G; Stremel, R W; Maldonado, C J; Werker, P M; Kon, M; Barker, J H

1999-05-01

In conventional dynamic myoplasties, the force generation is poorly controlled. This causes unnecessary fatigue of the transposed/transplanted electrically stimulated muscles and causes damage to the involved tissues. We introduced sequential segmental neuromuscular stimulation (SSNS) to reduce muscle fatigue by allowing part of the muscle to rest periodically while the other parts work. Despite this improvement, we hypothesize that fatigue could be further reduced in some applications of dynamic myoplasty if the muscles were made to contract according to need. The first necessary step is to gain appropriate control over the contractile activity of the dynamic myoplasty. Therefore, closed-loop control was tested on a sequentially stimulated neosphincter to strive for the best possible control over the amount of generated pressure. A selection of parameters was validated for optimizing control. We concluded that the frequency of corrections, the threshold for corrections, and the transition time are meaningful parameters in the controlling algorithm of the closed-loop control in a sequentially stimulated myoplasty.

Comparison of Image Quality and Radiation Dose of Coronary Computed Tomography Angiography Between Conventional Helical Scanning and a Strategy Incorporating Sequential Scanning

PubMed Central

Einstein, Andrew J.; Wolff, Steven D.; Manheimer, Eric D.; Thompson, James; Terry, Sylvia; Uretsky, Seth; Pilip, Adalbert; Peters, M. Robert

2009-01-01

Radiation dose from coronary computed tomography angiography may be reduced using a sequential scanning protocol rather than a conventional helical scanning protocol. Here we compare radiation dose and image quality from coronary computed tomography angiography in a single center between an initial period during which helical scanning with electrocardiographically-controlled tube current modulation was used for all patients (n=138) and after adoption of a strategy incorporating sequential scanning whenever appropriate (n=261). Using the sequential-if-appropriate strategy, sequential scanning was employed in 86.2% of patients. Compared to the helical-only strategy, this strategy was associated with a 65.1% dose reduction (mean dose-length product of 305.2 vs. 875.1 and mean effective dose of 14.9 mSv vs. 5.2 mSv, respectively), with no significant change in overall image quality, step artifacts, motion artifacts, or perceived image noise. For the 225 patients undergoing sequential scanning, the dose-length product was 201.9 ± 90.0 mGy·cm, while for patients undergoing helical scanning under either strategy, the dose-length product was 890.9 ± 293.3 mGy·cm (p<0.0001), corresponding to mean effective doses of 3.4 mSv and 15.1 mSv, respectively, a 77.5% reduction. Image quality was significantly greater for the sequential studies, reflecting the poorer image quality in patients undergoing helical scanning in the sequential-if-appropriate strategy. In conclusion, a sequential-if-appropriate diagnostic strategy reduces dose markedly compared to a helical-only strategy, with no significant difference in image quality. PMID:19892048

Activation of HIV Transcription by the Viral Tat Protein Requires a Demethylation Step Mediated by Lysine-specific Demethylase 1 (LSD1/KDM1)

PubMed Central

Sakane, Naoki; Kwon, Hye-Sook; Pagans, Sara; Kaehlcke, Katrin; Mizusawa, Yasuhiro; Kamada, Masafumi; Lassen, Kara G.; Chan, Jonathan; Greene, Warner C.; Schnoelzer, Martina; Ott, Melanie

2011-01-01

The essential transactivator function of the HIV Tat protein is regulated by multiple posttranslational modifications. Although individual modifications are well characterized, their crosstalk and dynamics of occurrence during the HIV transcription cycle remain unclear. We examine interactions between two critical modifications within the RNA-binding domain of Tat: monomethylation of lysine 51 (K51) mediated by Set7/9/KMT7, an early event in the Tat transactivation cycle that strengthens the interaction of Tat with TAR RNA, and acetylation of lysine 50 (K50) mediated by p300/KAT3B, a later process that dissociates the complex formed by Tat, TAR RNA and the cyclin T1 subunit of the positive transcription elongation factor b (P-TEFb). We find K51 monomethylation inhibited in synthetic Tat peptides carrying an acetyl group at K50 while acetylation can occur in methylated peptides, albeit at a reduced rate. To examine whether Tat is subject to sequential monomethylation and acetylation in cells, we performed mass spectrometry on immunoprecipitated Tat proteins and generated new modification-specific Tat antibodies against monomethylated/acetylated Tat. No bimodified Tat protein was detected in cells pointing to a demethylation step during the Tat transactivation cycle. We identify lysine-specific demethylase 1 (LSD1/KDM1) as a Tat K51-specific demethylase, which is required for the activation of HIV transcription in latently infected T cells. LSD1/KDM1 and its cofactor CoREST associates with the HIV promoter in vivo and activate Tat transcriptional activity in a K51-dependent manner. In addition, small hairpin RNAs directed against LSD1/KDM1 or inhibition of its activity with the monoamine oxidase inhibitor phenelzine suppresses the activation of HIV transcription in latently infected T cells. Our data support the model that a LSD1/KDM1/CoREST complex, normally known as a transcriptional suppressor, acts as a novel activator of HIV transcription through demethylation of K51 in Tat. Small molecule inhibitors of LSD1/KDM1 show therapeutic promise by enforcing HIV latency in infected T cells. PMID:21876670

Bartonella entry mechanisms into mammalian host cells.

PubMed

Eicher, Simone C; Dehio, Christoph

2012-08-01

The Gram-negative genus Bartonella comprises arthropod-borne pathogens that typically infect mammals in a host-specific manner. Bartonella bacilliformis and Bartonella quintana are human-specific pathogens, while several zoonotic bartonellae specific for diverse animal hosts infect humans as an incidental host. Clinical manifestations of Bartonella infections range from mild symptoms to life-threatening disease. Following transmission by blood-sucking arthropods or traumatic contact with infected animals, bartonellae display sequential tropisms towards endothelial and possibly other nucleated cells and erythrocytes, the latter in a host-specific manner. Attachment to the extracellular matrix (ECM) and to nucleated cells is mediated by surface-exposed bacterial adhesins, in particular trimeric autotransporter adhesins (TAAs). The subsequent engulfment of the pathogen into a vacuolar structure follows a unique series of events whereby the pathogen avoids the endolysosomal compartments. For Bartonella henselae and assumingly most other species, the infection process is aided at different steps by Bartonella effector proteins (Beps). They are injected into host cells through the type IV secretion system (T4SS) VirB/D4 and subvert host cellular functions to favour pathogen uptake. Bacterial binding to erythrocytes is mediated by Trw, another T4SS, in a strictly host-specific manner, followed by pathogen-forced uptake involving the IalB invasin and subsequent replication and persistence within a membrane-bound intra-erythrocytic compartment. © 2012 Blackwell Publishing Ltd.

Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.

PubMed

Tull, Samantha P; Yates, Clara M; Maskrey, Benjamin H; O'Donnell, Valerie B; Madden, Jackie; Grimble, Robert F; Calder, Philip C; Nash, Gerard B; Rainger, G Ed

2009-08-01

Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-alpha, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA), arachidonic acid, into the eicosanoid prostaglandin-D(2) (PGD(2)) by cyclooxygenase (COX) enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA), was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD(3). This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD(2) receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD(2) signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not only revealed an unsuspected level of regulation in the migration of inflammatory leukocytes, it also contributes to our understanding of the interactions of this bioactive lipid with the inflammatory system. Moreover, it indicates the potential for novel therapeutics that target the inflammatory system with greater affinity and/or specificity than supplementing the diet with n-3-PUFAs.

Post-processing techniques to enhance reliability of assignment algorithm based performance measures.

DOT National Transportation Integrated Search

2011-01-01

This study develops an enhanced transportation planning framework by augmenting the sequential four-step : planning process with post-processing techniques. The post-processing techniques are incorporated through a feedback : mechanism and aim to imp...

Evaluating specificity of sequential extraction for chemical forms of lead in artificially-contaminated and field-contaminated soils.

PubMed

Tai, Yiping; McBride, Murray B; Li, Zhian

2013-03-30

In the present study, we evaluated a commonly employed modified Bureau Communautaire de Référence (BCR test) 3-step sequential extraction procedure for its ability to distinguish forms of solid-phase Pb in soils with different sources and histories of contamination. When the modified BCR test was applied to mineral soils spiked with three forms of Pb (pyromorphite, hydrocerussite and nitrate salt), the added Pb was highly susceptible to dissolution in the operationally-defined "reducible" or "oxide" fraction regardless of form. When three different materials (mineral soil, organic soil and goethite) were spiked with soluble Pb nitrate, the BCR sequential extraction profiles revealed that soil organic matter was capable of retaining Pb in more stable and acid-resistant forms than silicate clay minerals or goethite. However, the BCR sequential extraction for field-collected soils with known and different sources of Pb contamination was not sufficiently discriminatory in the dissolution of soil Pb phases to allow soil Pb forms to be "fingerprinted" by this method. It is concluded that standard sequential extraction procedures are probably not very useful in predicting lability and bioavailability of Pb in contaminated soils. Copyright © 2013 Elsevier B.V. All rights reserved.

Tubing-Electrospinning: A One-Step Process for Fabricating Fibrous Matrices with Spatial, Chemical, and Mechanical Gradients.

PubMed

Kim, Jung-Suk; Im, Byung Gee; Jin, Gyuhyung; Jang, Jae-Hyung

2016-08-31

Guiding newly generated tissues in a gradient pattern, thereby precisely mimicking inherent tissue morphology and subsequently arranging the intimate networks between adjacent tissues, is essential to raise the technical levels of tissue engineering and facilitate its transition into the clinic. In this study, a straightforward electrospinning method (the tubing-electrospinning technique) was developed to create fibrous matrices readily with diverse gradient patterns and to induce patterned cellular responses. Gradient fibrous matrices can be produced simply by installing a series of polymer-containing lengths of tubing into an electrospinning circuit and sequentially processing polymers without a time lag. The loading of polymer samples with different characteristics, including concentration, wettability, and mechanical properties, into the tubing system enabled unique features in fibrous matrices, such as longitudinal gradients in fiber density, surface properties, and mechanical stiffness. The resulting fibrous gradients were shown to arrange cellular migration and residence in a gradient manner, thereby offering efficient cues to mediate patterned tissue formation. The one-step process using tubing-electrospinning apparatus can be used without significant modifications regardless of the type of fibrous gradient. Hence, the tubing-electrospinning system can serve as a platform that can be readily used by a wide-range of users to induce patterned tissue formation in a gradient manner, which will ultimately improve the functionality of tissue engineering scaffolds.

Elimination of sucrose transport and hydrolysis in Saccharomyces cerevisiae: a platform strain for engineering sucrose metabolism

PubMed Central

Marques, Wesley Leoricy; Mans, Robert; Marella, Eko Roy; Cordeiro, Rosa Lorizolla; van den Broek, Marcel; Daran, Jean-Marc G.; Pronk, Jack T.; Gombert, Andreas K.; van Maris, Antonius J.A.

2017-01-01

Abstract Many relevant options to improve efficacy and kinetics of sucrose metabolism in Saccharomyces cerevisiae and, thereby, the economics of sucrose-based processes remain to be investigated. An essential first step is to identify all native sucrose-hydrolysing enzymes and sucrose transporters in this yeast, including those that can be activated by suppressor mutations in sucrose-negative strains. A strain in which all known sucrose-transporter genes (MAL11, MAL21, MAL31, MPH2, MPH3) were deleted did not grow on sucrose after 2 months of incubation. In contrast, a strain with deletions in genes encoding sucrose-hydrolysing enzymes (SUC2, MAL12, MAL22, MAL32) still grew on sucrose. Its specific growth rate increased from 0.08 to 0.25 h−1 after sequential batch cultivation. This increase was accompanied by a 3-fold increase of in vitro sucrose-hydrolysis and isomaltase activities, as well as by a 3- to 5-fold upregulation of the isomaltase-encoding genes IMA1 and IMA5. One-step Cas9-mediated deletion of all isomaltase-encoding genes (IMA1-5) completely abolished sucrose hydrolysis. Even after 2 months of incubation, the resulting strain did not grow on sucrose. This sucrose-negative strain can be used as a platform to test metabolic engineering strategies and for fundamental studies into sucrose hydrolysis or transport. PMID:28087672

The Relationship between Authoritarian Leadership and Employees' Deviant Workplace Behaviors: The Mediating Effects of Psychological Contract Violation and Organizational Cynicism.

PubMed

Jiang, Hongyan; Chen, Yang; Sun, Peizhen; Yang, Jun

2017-01-01

This study investigated the relationship between authoritarian leadership and employees' deviant workplace behaviors (DWB), as well as the mediating effects of psychological contract violation and organizational cynicism. A cross-sectional survey was conducted among 391 manufacturing workers in a northern city of China. Structural equation modeling was performed to test the theory-driven models. The results showed that the relationship between authoritarian leadership and employees' DWB was mediated by organizational cynicism. Moreover, this relationship was also sequentially mediated by psychological contract violation and organizational cynicism. This research unveiled psychological contract violation and organizational cynicism as underlying mechanism that explained the link between authoritarian leadership and employees' DWB.

Microcomputer Software Engineering, Documentation and Evaluation

DTIC Science & Technology

1981-03-31

local dealer or call for complete specificalons. eAUTOMATIC INC To proceed step by step, we need toUe G T A TOMA IC NC. know where we are going and a...MICROPROCESSOR normal sequence that should be DIRECT MEMORY ACCESS preserved in the documentation. For INTRODUCTION 2.2 DRIVE CONTROLS example, you...with linear, sequential logic (like a computer). It is also the verbal side and controls language. The right side specializes in images, music, pictures

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases

PubMed Central

Rhodes, Lesley E.; Gledhill, Karl; Masoodi, Mojgan; Haylett, Ann K.; Brownrigg, Margaret; Thody, Anthony J.; Tobin, Desmond J.; Nicolaou, Anna

2009-01-01

Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI-MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and leukocyte markers, while quantifying clinical erythema. We show that vasodilatory prostaglandins (PGs) PGE2, PGF2α, and PGE3 accompany the erythema in the first 24–48 h, associated with increased COX-2 expression at 24 h. Novel, potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Sunburn is characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.—Rhodes, L. E., Gledhill, K., Masoodi, M., Haylett, A. K., Brownrigg, M., Thody, A. J., Tobin, D. J., Nicolaou, A. The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases. PMID:19584301

Efficacy and Safety of a Novel Three-Step Medial Release Technique in Varus Total Knee Arthroplasty.

PubMed

Kim, Min Woo; Koh, In Jun; Kim, Ju Hwan; Jung, Jae Jong; In, Yong

2015-09-01

We investigated the efficacy and safety of our novel three-step medial release technique in varus total knee arthroplasty (TKA) over time. Two hundred sixty seven consecutive varus TKAs were performed by applying the algorithmic release technique which consisted of sequential release of the deep medial collateral ligament (step 1), the semimembranosus (step 2), and multiple needle puncturing of the superficial medial collateral ligament (step 3). One hundred seventeen, 114, and 36 knees were balanced after step 1, 2, and 3 releases, respectively. There were no significant differences in changes of medial and lateral laxities between groups in over a year. Our novel stepwise medial release technique was efficacious and safe in balancing varus knees during TKA. Copyright © 2015 Elsevier Inc. All rights reserved.

40 CFR 63.522 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Hazardous Air Pollutants for Epoxy Resins Production and Non-Nylon Polyamides Production § 63.522... that are related to the production of BLR or WSR, including process vents, storage tanks, wastewater... process involving the bulk movement of material through sequential manufacturing steps. Mass, temperature...

Sequential Reactions of Surface-Tethered Glycolytic Enzymes

PubMed Central

Mukai, Chinatsu; Bergkvist, Magnus; Nelson, Jacquelyn L.; Travis, Alexander J.

2014-01-01

SUMMARY The development of complex hybrid organic-inorganic devices faces several challenges, including how they can generate energy. Cells face similar challenges regarding local energy production. Mammalian sperm solve this problem by generating ATP down the flagellar principal piece by means of glycolytic enzymes, several of which are tethered to a cytoskeletal support via germ cell-specific targeting domains. Inspired by this design, we have produced recombinant hexokinase type 1 and glucose-6-phosphate isomerase capable of oriented immobilization on a nickel-nitrilotriacetic acid modified surface. Specific activities of enzymes tethered via this strategy were substantially higher than when randomly adsorbed. Furthermore, these enzymes showed sequential activities when tethered onto the same surface. This is the first demonstration of surface-tethered pathway components showing sequential enzymatic activities, and it provides a first step toward reconstitution of glycolysis on engineered hybrid devices. PMID:19778729

Sequential microfluidic droplet processing for rapid DNA extraction.

PubMed

Pan, Xiaoyan; Zeng, Shaojiang; Zhang, Qingquan; Lin, Bingcheng; Qin, Jianhua

2011-11-01

This work describes a novel droplet-based microfluidic device, which enables sequential droplet processing for rapid DNA extraction. The microdevice consists of a droplet generation unit, two reagent addition units and three droplet splitting units. The loading/washing/elution steps required for DNA extraction were carried out by sequential microfluidic droplet processing. The movement of superparamagnetic beads, which were used as extraction supports, was controlled with magnetic field. The microdevice could generate about 100 droplets per min, and it took about 1 min for each droplet to perform the whole extraction process. The extraction efficiency was measured to be 46% for λ-DNA, and the extracted DNA could be used in subsequent genetic analysis such as PCR, demonstrating the potential of the device for fast DNA extraction. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Domino Way to Heterocycles

PubMed Central

Padwa, Albert; Bur, Scott K.

2007-01-01

Sequential transformations enable the facile synthesis of complex target molecules from simple building blocks in a single preparative step. Their value is amplified if they also create multiple stereogenic centers. In the ongoing search for new domino processes, emphasis is usually placed on sequential reactions which occur cleanly and without forming by-products. As a prerequisite for an ideally proceeding one-pot sequential transformation, the reactivity pattern of all participating components has to be such that each building block gets involved in a reaction only when it is supposed to do so. The development of sequences that combine transformations of fundamentally different mechanisms broadens the scope of such procedures in synthetic chemistry. This mini review contains a representative sampling from the last 15 years on the kinds of reactions that have been sequenced into cascades to produce heterocyclic molecules. PMID:17940591

Process for the production of ultrahigh purity silane with recycle from separation columns

NASA Technical Reports Server (NTRS)

Coleman, Larry M. (Inventor)

1982-01-01

Tri- and dichlorosilanes formed by hydrogenation in the course of the reaction of metallurgical silicon, hydrogen and recycle silicon tetrachloride are employed as feed into a separation column arrangement of sequential separation columns and redistribution reactors which processes the feed into ultrahigh purity silane and recycle silicon tetrachloride. A slip stream is removed from the bottom of two sequential columns and added to the recycle silicon tetrachloride process stream causing impurities in the slip streams to be subjected to reactions in the hydrogenation step whereby waste materials can be formed and readily separated.

Process for the production of ultrahigh purity silane with recycle from separation columns

DOEpatents

Coleman, Larry M.

1982-07-20

Tri- and dichlorosilanes formed by hydrogenation in the course of the reaction of metallurgical silicon, hydrogen and recycle silicon tetrachloride are employed as feed into a separation column arrangement of sequential separation columns and redistribution reactors which processes the feed into ultrahigh purity silane and recycle silicon tetrachloride. A slip stream is removed from the bottom of two sequential columns and added to the recycle silicon tetrachloride process stream causing impurities in the slip streams to be subjected to reactions in the hydrogenation step whereby waste materials can be formed and readily separated.

Sequential cancer immunotherapy: targeted activity of dimeric TNF and IL-8

PubMed Central

Adrian, Nicole; Siebenborn, Uta; Fadle, Natalie; Plesko, Margarita; Fischer, Eliane; Wüest, Thomas; Stenner, Frank; Mertens, Joachim C.; Knuth, Alexander; Ritter, Gerd; Old, Lloyd J.; Renner, Christoph

2009-01-01

Polymorphonuclear neutrophils (PMNs) are potent effectors of inflammation and their attempts to respond to cancer are suggested by their systemic, regional and intratumoral activation. We previously reported on the recruitment of CD11b+ leukocytes due to tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP). However, TNF-induced chemo-attraction and extravasation of PMNs from blood into the tumor is a multistep process essentially mediated by interleukin 8. With the aim to amplify the TNF-induced and IL-8-mediated chemotactic response, we generated immunocytokines by N-terminal fusion of a human anti-FAP scFv fragment with human IL-8 (IL-872) and its N-terminally truncated form IL-83-72. Due to the dramatic difference in chemotaxis induction in vitro, we favored the mature chemokine fused to the anti-FAP scFv for further investigation in vivo. BALB/c nu/nu mice were simultaneously xenografted with FAP-positive or -negative tumors and extended chemo-attraction of PMNs was only detectable in FAP-expressing tissue after intravenous administration of the anti-FAP scFv-IL-872 construct. As TNF-activated PMNs are likewise producers and primary targets for IL-8, we investigated the therapeutic efficacy of co-administration of both effectors: Sequential application of scFv-IL-872 and dimeric IgG1-TNF fusion proteins significantly enhanced anti-tumor activity when compared either to a single effector treatment regimen or sequential application of non-targeted cytokines, indicating that the tumor-restricted sequential application of IL-872 and TNF is a promising approach for cancer therapy. PMID:19267427

Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and sepsis.

PubMed

Keller, Steve A; Paxian, Marcus; Lee, Sun M; Clemens, Mark G; Huynh, Toan

2005-03-01

Prostaglandins, synthesized by cyclooxygenase (COX), play an important role in the pathophysiology of inflammation. Severe injuries result in immunosuppression, mediated, in part, by maladaptive changes in macrophages. Herein, we assessed Kupffer cell-mediated cyclooxygenase-2 (COX-2) expression on liver function and damage after trauma and sepsis. To ablate Kupffer cells, Sprague Dawley rats were treated with gadolinium chloride (GdCl3) 48 and 24 h before experimentation. Animals then underwent femur fracture (FFx) followed 48 h later by cecal ligation and puncture (CLP). Controls received sham operations. After 24 h, liver samples were obtained, and mRNA and protein expression were determined by PCR, Western blot, and immunohistochemistry. Indocyanine-Green (ICG) clearance and plasma alanine aminotransferase (ALT) levels were determined to assess liver function and damage, respectively. One-way analysis of variance (ANOVA) with Student-Newman-Keuls test was used to assess statistical significance. After CLP alone, FFx+CLP, and GdCl3+FFx+CLP, clearance of ICG decreased. Plasma ALT levels increased in parallel with severity of injury. Kupffer cell depletion attenuated the increased ALT levels after FFx+CLP. Femur fracture alone did not alter COX-2 protein compared with sham. By contrast, COX-2 protein increased after CLP and was potentiated by sequential stress. Again, Kupffer cell depletion abrogated the increase in COX-2 after sequential stress. Immunohistochemical data confirmed COX-2 positive cells to be Kupffer cells. In this study, sequential stress increased hepatic COX-2 protein. Depletion of Kupffer cells reduced COX-2 and attenuated hepatocellular injuries. Our data suggest that Kupffer cell-dependent pathways may contribute to the inflammatory response leading to increased mortality after sequential stress.

Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis

PubMed Central

Garg, Ankur; Gotoh, Noriko; Feng, Gen-Sheng; Zhong, Jian; Wang, Fen; Kariminejad, Ariana; Brooks, Steven

2017-01-01

The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development. PMID:29028795

Monitoring proteins using in vivo near-infrared time-domain optical imaging after 2-O-hexyldiglycerol-mediated transfer to the brain.

PubMed

Hülper, Petra; Dullin, Christian; Kugler, Wilfried; Lakomek, Max; Erdlenbruch, Bernhard

2011-04-01

The aim of the present study was to gain insight into the penetration, biodistribution, and fate of globulins in the brain after 2-O-hexyldiglycerol-induced blood-brain barrier opening. The spatial distribution of fluorescence probes was investigated after blood-brain barrier opening with intracarotid 2-O-hexyldiglycerol injection. Fluorescence intensity was visualized by microscopy (mice and rats) and by in vivo time-domain optical imaging. There was an increased 2-O-hexyldiglycerol-mediated transfer of fluorescence-labeled globulins into the ipsilateral hemisphere. Sequential in vivo measurements revealed that the increase in protein concentration lasted at least 96 h after administration. Ex vivo detection of tissue fluorescence confirmed the results obtained in vivo. Globulins enter the healthy brain in conjunction with 2-O-hexyldiglycerol. Sequential in vivo near-infrared fluorescence measurements enable the visualization of the spatial distribution of antibodies in the brain of living small animals.

Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis.

PubMed

Garg, Ankur; Bansal, Mukesh; Gotoh, Noriko; Feng, Gen-Sheng; Zhong, Jian; Wang, Fen; Kariminejad, Ariana; Brooks, Steven; Zhang, Xin

2017-10-01

The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development.

Part Singing Revisited.

ERIC Educational Resources Information Center

Junda, Mary Ellen

1997-01-01

Maintains that children's success with drones, responsorial singing, and ostinatos in the primary grades can lead naturally to the singing of polyphony and homophony in the upper elementary grades. Recommends teachers using age-appropriate materials, teaching sequentially, and evaluating each instructional step. Lists national standards related to…

Synthetic nat- or ent-steroids in as few as five chemical steps from epichlorohydrin

NASA Astrophysics Data System (ADS)

Kim, Wan Shin; Du, Kang; Eastman, Alan; Hughes, Russell P.; Micalizio, Glenn C.

2018-01-01

Today, more than 100 Food and Drug Administration-approved steroidal agents are prescribed daily for indications including heart failure, inflammation, pain and cancer. While triumphs in organic chemistry have enabled the establishment and sustained growth of the steroid pharmaceutical industry, the production of highly functionalized synthetic steroids of varying substitution and stereochemistry remains challenging, despite the numerous reports of elegant strategies for their de novo synthesis. Here, we describe an advance in chemical synthesis that has established an enantiospecific means to access novel steroids with unprecedented facility and flexibility through the sequential use of two powerful ring-forming reactions: a modern metallacycle-mediated annulative cross-coupling and a new acid-catalysed vinylcyclopropane rearrangement cascade. In addition to accessing synthetic steroids of either enantiomeric series, these steroidal products have been selectively functionalized within each of the four carbocyclic rings, a synthetic ent-steroid has been prepared on a multigram scale, the enantiomer of a selective oestrogen has been synthesized, and a novel ent-steroid with growth inhibitory properties in three cancer cell lines has been discovered.

Surface Structure Characterization of Aspergillus fumigatus Conidia Mutated in the Melanin Synthesis Pathway and Their Human Cellular Immune Response

PubMed Central

Bayry, Jagadeesh; Beaussart, Audrey; Dufrêne, Yves F.; Sharma, Meenu; Bansal, Kushagra; Kniemeyer, Olaf; Aimanianda, Vishukumar; Brakhage, Axel A.; Kaveri, Srini V.; Kwon-Chung, Kyung J.

2014-01-01

In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface. PMID:24818666

In vitro glucose uptake activity of Aegles marmelos and Syzygium cumini by activation of Glut-4, PI3 kinase and PPARgamma in L6 myotubes.

PubMed

Anandharajan, R; Jaiganesh, S; Shankernarayanan, N P; Viswakarma, R A; Balakrishnan, A

2006-06-01

The purpose of the present study is to investigate the effect of methanolic extracts of Aegles marmelos and Syzygium cumini on a battery of targets glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARgamma) and phosphatidylinositol 3' kinase (PI3 kinase) involved in glucose transport. A. marmelos and S. cumini are anti-diabetic medicinal plants being used in Indian traditional medicine. Different solvent extracts extracted sequentially were analysed for glucose uptake activity at each step and methanol extracts were found to be significantly active at 100ng/ml dose comparable with insulin and rosiglitazone. Elevation of Glut-4, PPARgamma and PI3 kinase by A. marmelos and S. cumini in association with glucose transport supported the up-regulation of glucose uptake. The inhibitory effect of cycloheximide on A. marmelos- and S. cumini-mediated glucose uptake suggested that new protein synthesis is required for the elevated glucose transport. Current observation concludes that methanolic extracts of A. marmelos and S. cumini activate glucose transport in a PI3 kinase-dependent fashion.

Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens1

PubMed Central

Tatsis, Nia; Lasaro, Marcio O.; Lin, Shih-Wen; Xiang, Zhi Q.; Zhou, Dongming; DiMenna, Lauren; Li, Hua; Bian, Ang; Abdulla, Sarah; Li, Yan; Giles-Davis, Wynetta; Engram, Jessica; Ratcliffe, Sarah J.; Silvestri, Guido; Ertl, Hildegund C.; Betts, Michael R.

2009-01-01

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with pre-existing neutralizing antibodies against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee derived Ad (AdC) vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the AdC vectors induced higher T and B cell responses than repeated immunizations with the AdHu5 vector especially in AdHu5-pre-exposed macaques. PMID:19414814

Two Distinct Mechanisms for C-C Desaturation by Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenases: Importance of α-Heteroatom Assistance.

PubMed

Dunham, Noah P; Chang, Wei-Chen; Mitchell, Andrew J; Martinie, Ryan J; Zhang, Bo; Bergman, Jonathan A; Rajakovich, Lauren J; Wang, Bo; Silakov, Alexey; Krebs, Carsten; Boal, Amie K; Bollinger, J Martin

2018-06-04

Hydroxylation of aliphatic carbons by nonheme Fe(IV)-oxo (ferryl) complexes proceeds by hydrogen-atom (H•) transfer (HAT) to the ferryl and subsequent coupling between the carbon radical and Fe(III)-coordinated oxygen (termed rebound). Enzymes that use H•-abstracting ferryl complexes for other transformations must either suppress rebound or further process hydroxylated intermediates. For olefin-installing C-C desaturations, it has been proposed that a second HAT to the Fe(III)-OH complex from the carbon α to the radical preempts rebound. Deuterium ( 2 H) at the second site should slow this step, potentially making rebound competitive. Desaturations mediated by two related l-arginine-modifying iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases behave oppositely in this key test, implicating different mechanisms. NapI, the l-Arg 4,5-desaturase from the naphthyridinomycin biosynthetic pathway, abstracts H• first from C5 but hydroxylates this site (leading to guanidine release) to the same modest extent whether C4 harbors 1 H or 2 H. By contrast, an unexpected 3,4-desaturation of l-homoarginine (l-hArg) by VioC, the l-Arg 3-hydroxylase from the viomycin biosynthetic pathway, is markedly disfavored relative to C4 hydroxylation when C3 (the second hydrogen donor) harbors 2 H. Anchimeric assistance by N6 permits removal of the C4-H as a proton in the NapI reaction, but, with no such assistance possible in the VioC desaturation, a second HAT step (from C3) is required. The close proximity (≤3.5 Å) of both l-hArg carbons to the oxygen ligand in an X-ray crystal structure of VioC harboring a vanadium-based ferryl mimic supports and rationalizes the sequential-HAT mechanism. The results suggest that, although the sequential-HAT mechanism is feasible, its geometric requirements may make competing hydroxylation unavoidable, thus explaining the presence of α-heteroatoms in nearly all native substrates for Fe/2OG desaturases.

A sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes.

PubMed

Li, Qiuhong; Hutchins, Andrew P; Chen, Yong; Li, Shengbiao; Shan, Yongli; Liao, Baojian; Zheng, Dejin; Shi, Xi; Li, Yinxiong; Chan, Wai-Yee; Pan, Guangjin; Wei, Shicheng; Shu, Xiaodong; Pei, Duanqing

2017-05-03

Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGFβ signalling followed by a MET process. Pharmacological inhibition of TGFβ signalling blocks the EMT as well as DE formation. We then identify SNAI1 as the key EMT transcriptional factor required for the specification of DE. Genetic ablation of SNAI1 in hESCs does not affect the maintenance of pluripotency or neural differentiation, but completely disrupts the formation of DE. These results reveal a critical mesenchymal phase during the acquisition of DE, highlighting a role for sequential EMT-METs in both differentiation and reprogramming.

Operative air temperature data for different measures applied on a building envelope in warm climate.

PubMed

Baglivo, Cristina; Congedo, Paolo Maria

2018-04-01

Several technical combinations have been evaluated in order to design high energy performance buildings for the warm climate. The analysis has been developed in several steps, avoiding the use of HVAC systems. The methodological approach of this study is based on a sequential search technique and it is shown on the paper entitled "Envelope Design Optimization by Thermal Modeling of a Building in a Warm Climate" [1]. The Operative Air Temperature trends (TOP), for each combination, have been plotted through a dynamic simulation performed using the software TRNSYS 17 (a transient system simulation program, University of Wisconsin, Solar Energy Laboratory, USA, 2010). Starting from the simplest building configuration consisting of 9 rooms (equal-sized modules of 5 × 5 m 2 ), the different building components are sequentially evaluated until the envelope design is optimized. The aim of this study is to perform a step-by-step simulation, simplifying as much as possible the model without making additional variables that can modify their performances. Walls, slab-on-ground floor, roof, shading and windows are among the simulated building components. The results are shown for each combination and evaluated for Brindisi, a city in southern Italy having 1083 degrees day, belonging to the national climatic zone C. The data show the trends of the TOP for each measure applied in the case study for a total of 17 combinations divided into eight steps.

Six Factors Inhibiting the Use of Peer Mediation in a Junior High School

ERIC Educational Resources Information Center

Theberge, Susan K.; Karan, Orv C.

2004-01-01

Schools have increasingly been implementing peer mediation programs as a way to help students find peaceful means for resolving conflicts (Casella, 2000). Peer mediation is a process in which students that have been taught a structured, step-by-step model assist others to peacefully negotiate solutions to their interpersonal conflicts. In spite of…

The Relationship between Authoritarian Leadership and Employees’ Deviant Workplace Behaviors: The Mediating Effects of Psychological Contract Violation and Organizational Cynicism

PubMed Central

Jiang, Hongyan; Chen, Yang; Sun, Peizhen; Yang, Jun

2017-01-01

This study investigated the relationship between authoritarian leadership and employees’ deviant workplace behaviors (DWB), as well as the mediating effects of psychological contract violation and organizational cynicism. A cross-sectional survey was conducted among 391 manufacturing workers in a northern city of China. Structural equation modeling was performed to test the theory-driven models. The results showed that the relationship between authoritarian leadership and employees’ DWB was mediated by organizational cynicism. Moreover, this relationship was also sequentially mediated by psychological contract violation and organizational cynicism. This research unveiled psychological contract violation and organizational cynicism as underlying mechanism that explained the link between authoritarian leadership and employees’ DWB. PMID:28536550

Self-compassion and physical health: Exploring the roles of perceived stress and health-promoting behaviors

PubMed Central

Homan, Kristin J; Sirois, Fuschia M

2017-01-01

Growing evidence indicates that self-compassion is associated with better physical health, but the pathways that mediate this relationship are not well understood. This study tested a serial mediation model that linked self-compassion, perceived stress, health behaviors, and a comprehensive index of physical health. A sample of 176 individuals completed an online survey posted on Amazon’s Mechanical Turk. Self-compassion had an indirect effect on physical health via both mediators and through the sequential pathway, suggesting that taking a kind, accepting and mindful stance toward one’s flaws and failures may have benefits for reducing stress and promoting health behaviors. PMID:29379620

Interleukin-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

PubMed Central

Liu, Rebecca; Lauridsen, Holly M.; Amezquita, Robert A.; Pierce, Richard W.; Jane-wit, Dan; Fang, Caodi; Pellowe, Amanda S.; Kirkiles-Smith, Nancy C.; Gonzalez, Anjelica L.; Pober, Jordan S.

2016-01-01

A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space. PMID:27534549

Novel regulation of Skp1 by the Dictyostelium AgtA α-galactosyltransferase involves the Skp1-binding activity of its WD40 repeat domain.

PubMed

Schafer, Christopher M; Sheikh, M Osman; Zhang, Dongmei; West, Christopher M

2014-03-28

The role of Skp1 as an adaptor protein that links Cullin-1 to F-box proteins in E3 Skp1/Cullin-1/F-box protein (SCF) ubiquitin ligases is well characterized. In the social amoeba Dictyostelium and probably many other unicellular eukaryotes, Skp1 is modified by a pentasaccharide attached to a hydroxyproline near its C terminus. This modification is important for oxygen-sensing during Dictyostelium development and is mediated by a HIF-α type prolyl 4-hydroxylase and five sequentially acting cytoplasmic glycosyltransferase activities. Gene disruption studies show that AgtA, the enzyme responsible for addition of the final two galactose residues, in α-linkages to the Skp1 core trisaccharide, is unexpectedly critical for oxygen-dependent terminal development. AgtA possesses a WD40 repeat domain C-terminal to its single catalytic domain and, by use of domain deletions, binding studies, and enzyme assays, we find that the WD40 repeats confer a salt-sensitive second-site binding interaction with Skp1 that mediates novel catalytic activation in addition to simple substrate recognition. In addition, AgtA binds similarly well to precursor isoforms of Skp1 by a salt-sensitive mechanism that competes with binding to an F-box protein and recognition by early modification enzymes, and the effect of binding is diminished when AgtA modifies Skp1. Genetic studies show that loss of AgtA is more severe when an earlier glycosylation step is blocked, and overexpressed AgtA is deleterious if catalytically inactivated. Together, the findings suggest that AgtA mediates non-enzymatic control of unmodified and substrate precursor forms of Skp1 by a binding mechanism that is normally relieved by switch-like activation of its glycosylation function.

Sequential growth for lifetime extension in biomimetic polypyrrole actuator systems

NASA Astrophysics Data System (ADS)

Sarrazin, J. C.; Mascaro, Stephen A.

2015-04-01

Electroactive polymers (EAPs) present prospective use in actuation and manipulation devices due to their low electrical activation requirements, biocompatibility, and mechanical performance. One of the main drawbacks with EAP actuators is a decrease in performance over extended periods of operation caused by over-oxidation of the polymer and general polymer degradation. Synthesis of the EAP material, polypyrrole with an embedded metal helix allows for sequential growth of the polymer during operation. The helical metal electrode acts as a scaffolding to support the polymer, and direct the 3-dimensional change in volume of the polymer along the axis of the helix during oxidative and reductive cycling. The metal helix also provides a working metal electrode through the entire length of the polymer actuator to distribute charge for actuation, as well as for sequential growth steps during the lifetime of operation of the polymer. This work demonstrates the method of sequential growth can be utilized after extended periods of use to partially restore electrical and mechanical performance of polypyrrole actuators. Since the actuation must be temporarily stopped to allow for a sequential growth cycle to be performed and reverse some of the polymer degradation, these actuator systems more closely mimic natural muscle in their analogous maintenance and repair.

Multigrid methods with space–time concurrency

DOE PAGES

Falgout, R. D.; Friedhoff, S.; Kolev, Tz. V.; ...

2017-10-06

Here, we consider the comparison of multigrid methods for parabolic partial differential equations that allow space–time concurrency. With current trends in computer architectures leading towards systems with more, but not faster, processors, space–time concurrency is crucial for speeding up time-integration simulations. In contrast, traditional time-integration techniques impose serious limitations on parallel performance due to the sequential nature of the time-stepping approach, allowing spatial concurrency only. This paper considers the three basic options of multigrid algorithms on space–time grids that allow parallelism in space and time: coarsening in space and time, semicoarsening in the spatial dimensions, and semicoarsening in the temporalmore » dimension. We develop parallel software and performance models to study the three methods at scales of up to 16K cores and introduce an extension of one of them for handling multistep time integration. We then discuss advantages and disadvantages of the different approaches and their benefit compared to traditional space-parallel algorithms with sequential time stepping on modern architectures.« less

Single step sequential polydimethylsiloxane wet etching to fabricate a microfluidic channel with various cross-sectional geometries

NASA Astrophysics Data System (ADS)

Wang, C.-K.; Liao, W.-H.; Wu, H.-M.; Lo, Y.-H.; Lin, T.-R.; Tung, Y.-C.

2017-11-01

Polydimethylsiloxane (PDMS) has become a widely used material to construct microfluidic devices for various biomedical and chemical applications due to its desirable material properties and manufacturability. PDMS microfluidic devices are usually fabricated using soft lithography replica molding methods with master molds made of photolithogrpahy patterned photoresist layers on silicon wafers. The fabricated microfluidic channels often have rectangular cross-sectional geometries with single or multiple heights. In this paper, we develop a single step sequential PDMS wet etching process that can be used to fabricate microfluidic channels with various cross-sectional geometries from single-layer PDMS microfluidic channels. The cross-sections of the fabricated channel can be non-rectangular, and varied along the flow direction. Furthermore, the fabricated cross-sectional geometries can be numerically simulated beforehand. In the experiments, we fabricate microfluidic channels with various cross-sectional geometries using the developed technique. In addition, we fabricate a microfluidic mixer with alternative mirrored cross-sectional geometries along the flow direction to demonstrate the practical usage of the developed technique.

Multigrid methods with space–time concurrency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Falgout, R. D.; Friedhoff, S.; Kolev, Tz. V.

Here, we consider the comparison of multigrid methods for parabolic partial differential equations that allow space–time concurrency. With current trends in computer architectures leading towards systems with more, but not faster, processors, space–time concurrency is crucial for speeding up time-integration simulations. In contrast, traditional time-integration techniques impose serious limitations on parallel performance due to the sequential nature of the time-stepping approach, allowing spatial concurrency only. This paper considers the three basic options of multigrid algorithms on space–time grids that allow parallelism in space and time: coarsening in space and time, semicoarsening in the spatial dimensions, and semicoarsening in the temporalmore » dimension. We develop parallel software and performance models to study the three methods at scales of up to 16K cores and introduce an extension of one of them for handling multistep time integration. We then discuss advantages and disadvantages of the different approaches and their benefit compared to traditional space-parallel algorithms with sequential time stepping on modern architectures.« less

Formation of Stone-Wales edge: Multistep reconstruction and growth mechanisms of zigzag nanographene.

PubMed

Dang, Jing-Shuang; Wang, Wei-Wei; Zheng, Jia-Jia; Nagase, Shigeru; Zhao, Xiang

2017-10-05

Although the existence of Stone-Wales (5-7) defect at graphene edge has been clarified experimentally, theoretical study on the formation mechanism is still imperfect. In particular, the regioselectivity of multistep reactions at edge (self-reconstruction and growth with foreign carbon feedstock) is essential to understand the kinetic behavior of reactive boundaries but investigations are still lacking. Herein, by using finite-sized models, multistep reconstructions and carbon dimer additions of a bared zigzag edge are introduced using density functional theory calculations. The zigzag to 5-7 transformation is proved as a site-selective process to generate alternating 5-7 pairs sequentially and the first step with largest barrier is suggested as the rate-determining step. Conversely, successive C 2 insertions on the active edge are calculated to elucidate the formation of 5-7 edge during graphene growth. A metastable intermediate with a triple sequentially fused pentagon fragment is proved as the key structure for 5-7 edge formation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sequential Extraction Results and Mineralogy of Mine Waste and Stream Sediments Associated With Metal Mines in Vermont, Maine, and New Zealand

USGS Publications Warehouse

Piatak, N.M.; Seal, R.R.; Sanzolone, R.F.; Lamothe, P.J.; Brown, Z.A.; Adams, M.

2007-01-01

We report results from sequential extraction experiments and the quantitative mineralogy for samples of stream sediments and mine wastes collected from metal mines. Samples were from the Elizabeth, Ely Copper, and Pike Hill Copper mines in Vermont, the Callahan Mine in Maine, and the Martha Mine in New Zealand. The extraction technique targeted the following operationally defined fractions and solid-phase forms: (1) soluble, adsorbed, and exchangeable fractions; (2) carbonates; (3) organic material; (4) amorphous iron- and aluminum-hydroxides and crystalline manganese-oxides; (5) crystalline iron-oxides; (6) sulfides and selenides; and (7) residual material. For most elements, the sum of an element from all extractions steps correlated well with the original unleached concentration. Also, the quantitative mineralogy of the original material compared to that of the residues from two extraction steps gave insight into the effectiveness of reagents at dissolving targeted phases. The data are presented here with minimal interpretation or discussion and further analyses and interpretation will be presented elsewhere.

Designing group sequential randomized clinical trials with time to event end points using a R function.

PubMed

Filleron, Thomas; Gal, Jocelyn; Kramar, Andrew

2012-10-01

A major and difficult task is the design of clinical trials with a time to event endpoint. In fact, it is necessary to compute the number of events and in a second step the required number of patients. Several commercial software packages are available for computing sample size in clinical trials with sequential designs and time to event endpoints, but there are a few R functions implemented. The purpose of this paper is to describe features and use of the R function. plansurvct.func, which is an add-on function to the package gsDesign which permits in one run of the program to calculate the number of events, and required sample size but also boundaries and corresponding p-values for a group sequential design. The use of the function plansurvct.func is illustrated by several examples and validated using East software. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Sequential shrink photolithography for plastic microlens arrays

NASA Astrophysics Data System (ADS)

Dyer, David; Shreim, Samir; Jayadev, Shreshta; Lew, Valerie; Botvinick, Elliot; Khine, Michelle

2011-07-01

Endeavoring to push the boundaries of microfabrication with shrinkable polymers, we have developed a sequential shrink photolithography process. We demonstrate the utility of this approach by rapidly fabricating plastic microlens arrays. First, we create a mask out of the children's toy Shrinky Dinks by simply printing dots using a standard desktop printer. Upon retraction of this pre-stressed thermoplastic sheet, the dots shrink to a fraction of their original size, which we then lithographically transfer onto photoresist-coated commodity shrink wrap film. This shrink film reduces in area by 95% when briefly heated, creating smooth convex photoresist bumps down to 30 µm. Taken together, this sequential shrink process provides a complete process to create microlenses, with an almost 99% reduction in area from the original pattern size. Finally, with a lithography molding step, we emboss these bumps into optical grade plastics such as cyclic olefin copolymer for functional microlens arrays.

Sequential shrink photolithography for plastic microlens arrays.

PubMed

Dyer, David; Shreim, Samir; Jayadev, Shreshta; Lew, Valerie; Botvinick, Elliot; Khine, Michelle

2011-07-18

Endeavoring to push the boundaries of microfabrication with shrinkable polymers, we have developed a sequential shrink photolithography process. We demonstrate the utility of this approach by rapidly fabricating plastic microlens arrays. First, we create a mask out of the children's toy Shrinky Dinks by simply printing dots using a standard desktop printer. Upon retraction of this pre-stressed thermoplastic sheet, the dots shrink to a fraction of their original size, which we then lithographically transfer onto photoresist-coated commodity shrink wrap film. This shrink film reduces in area by 95% when briefly heated, creating smooth convex photoresist bumps down to 30 µm. Taken together, this sequential shrink process provides a complete process to create microlenses, with an almost 99% reduction in area from the original pattern size. Finally, with a lithography molding step, we emboss these bumps into optical grade plastics such as cyclic olefin copolymer for functional microlens arrays.

Sequential shrink photolithography for plastic microlens arrays

PubMed Central

Dyer, David; Shreim, Samir; Jayadev, Shreshta; Lew, Valerie; Botvinick, Elliot; Khine, Michelle

2011-01-01

Endeavoring to push the boundaries of microfabrication with shrinkable polymers, we have developed a sequential shrink photolithography process. We demonstrate the utility of this approach by rapidly fabricating plastic microlens arrays. First, we create a mask out of the children’s toy Shrinky Dinks by simply printing dots using a standard desktop printer. Upon retraction of this pre-stressed thermoplastic sheet, the dots shrink to a fraction of their original size, which we then lithographically transfer onto photoresist-coated commodity shrink wrap film. This shrink film reduces in area by 95% when briefly heated, creating smooth convex photoresist bumps down to 30 µm. Taken together, this sequential shrink process provides a complete process to create microlenses, with an almost 99% reduction in area from the original pattern size. Finally, with a lithography molding step, we emboss these bumps into optical grade plastics such as cyclic olefin copolymer for functional microlens arrays. PMID:21863126

Definition of molecular determinants of prostate cancer cell bone extravasation.

PubMed

Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J

2013-01-15

Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

Pathways to Hazardous Drinking Among Racially and Socioeconomically Diverse Lesbian Women: Sexual Minority Stress, Rumination, Social Isolation, and Drinking to Cope

PubMed Central

Lewis, Robin J.; Mason, Tyler B.; Winstead, Barbara A.; Gaskins, Melissa; Irons, Lance B.

2016-01-01

Lesbian women engage in more hazardous drinking than heterosexual women yet we know relatively little about what explains this disparity. In the present study, race, socioeconomic status, minority stress, general psychological processes and distress were examined as pathways to hazardous drinking among young (18-35 years) Black and non-Hispanic White lesbian women. We used the psychological mediation framework adaptation of minority stress theory and the reserve capacity model as theoretical underpinnings of the conceptual model in the current study. Self-identified lesbian participants (N= 867) completed a one-time online survey that assessed race, socioeconomic status, perceived sexual minority discrimination, proximal minority stress (concealment, internalized homophobia, lack of connection to lesbian community), rumination, social isolation, psychological distress, drinking to cope, and hazardous drinking. Cross-sectional results demonstrated that being Black was associated with hazardous drinking via sequential mediators of rumination, psychological distress, and drinking to cope. Socioeconomic status was associated with hazardous drinking via sequential mediators of sexual minority discrimination, proximal minority stress, rumination, social isolation, psychological distress, and drinking to cope. Understanding these pathways can aid researchers and clinicians studying and working with lesbians who are at risk for hazardous drinking. PMID:28138208

Phytohormone mediation of interactions between herbivores and plant pathogens.

PubMed

Lazebnik, Jenny; Frago, Enric; Dicke, Marcel; van Loon, Joop J A

2014-07-01

Induced plant defenses against either pathogens or herbivore attackers are regulated by phytohormones. These phytohormones are increasingly recognized as important mediators of interactions between organisms associated with plants. In this review, we discuss the role of plant defense hormones in sequential tri-partite interactions among plants, pathogenic microbes, and herbivorous insects, based on the most recent literature. We discuss the importance of pathogen trophic strategy in the interaction with herbivores that exhibit different feeding modes. Plant resistance mechanisms also affect plant quality in future interactions with attackers. We discuss exemplary evidence for the hypotheses that (i) biotrophic pathogens can facilitate chewing herbivores, unless plants exhibit effector-triggered immunity, but (ii) facilitate or inhibit phloem feeders. (iii) Necrotrophic pathogens, on the other hand, can inhibit both phloem feeders and chewers. We also propose herbivore feeding mode as predictor of effects on pathogens of different trophic strategies, providing evidence for the hypotheses that (iv) phloem feeders inhibit pathogen attack by increasing SA induction, whereas (v) chewing herbivores tend not to affect necrotrophic pathogens, while they may either inhibit or facilitate biotrophic pathogens. Putting these hypotheses to the test will increase our understanding of phytohormonal regulation of plant defense to sequential attack by plant pathogens and insect herbivores. This will provide valuable insight into plant-mediated ecological interactions among members of the plant-associated community.

Mothers' Knowledge of Early Adolescents' Activities following the Middle School Transition and Pubertal Maturation

ERIC Educational Resources Information Center

Laird, Robert D.; Marrero, Matthew D.

2011-01-01

This study tested a sequential mediation model to determine whether experiences, social cognitions, or parent-adolescent interactional processes account for lower levels of mothers' knowledge of adolescents' whereabouts and activities following early adolescents' transition into middle school (MS) and pubertal development. Cross-sectional data…

Synthesis of the carbocyclic core of the cornexistins by ring-closing metathesis.

PubMed

Clark, J Stephen; Marlin, Frederic; Nay, Bastien; Wilson, Claire

2003-01-09

An advanced intermediate in the synthesis of the phytotoxins cornexistin and hydroxycornexistin has been synthesized. Sequential palladium-mediated sp(2)-sp(3) fragment coupling and ring-closing diene metathesis have been used to construct the nine-membered carbocyclic core found in the natural products. [reaction--see text

Support, Belonging, Motivation, and Engagement in the College Classroom: A Mixed Method Study

ERIC Educational Resources Information Center

Zumbrunn, Sharon; McKim, Courtney; Buhs, Eric; Hawley, Leslie R.

2014-01-01

This explanatory sequential mixed methods study examined how belonging perceptions, academic motivation, and engagement might mediate the relationship between academic contextual characteristics and achievement using structural equation modeling and qualitative follow-up interviews with college students from a large, Midwestern university. In the…

Amyloid Beta Mediates Memory Formation

ERIC Educational Resources Information Center

Garcia-Osta, Ana; Alberini, Cristina M.

2009-01-01

The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid [beta] (1-42) peptide (A[beta][1-42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated,…

Adolescents' Religiousness and Substance Use Are Linked via Afterlife Beliefs and Future Orientation

ERIC Educational Resources Information Center

Holmes, Christopher; Kim-Spoon, Jungmeen

2017-01-01

Although religiousness has been identified as a protective factor against adolescent substance use, processes through which these effects may operate are unclear. The current longitudinal study examined sequential mediation of afterlife beliefs and future orientation in the relation between adolescent religiousness and cigarette, alcohol, and…

One-step detection of microRNA with high sensitivity and specificity via target-triggered loop-mediated isothermal amplification (TT-LAMP).

PubMed

Sun, Yuanyuan; Tian, Hui; Liu, Chenghui; Sun, Yueying; Li, Zhengping

2017-10-05

A novel one-step microRNA assay is developed based on a target-triggered loop-mediated isothermal amplification (TT-LAMP) mechanism, which enables the accurate detection of as low as 100 aM (1 zmol) microRNA with simple one-step operation by using only one-type of DNA polymerase.

Efficient feature subset selection with probabilistic distance criteria. [pattern recognition

NASA Technical Reports Server (NTRS)

Chittineni, C. B.

1979-01-01

Recursive expressions are derived for efficiently computing the commonly used probabilistic distance measures as a change in the criteria both when a feature is added to and when a feature is deleted from the current feature subset. A combinatorial algorithm for generating all possible r feature combinations from a given set of s features in (s/r) steps with a change of a single feature at each step is presented. These expressions can also be used for both forward and backward sequential feature selection.

Deferred discrimination algorithm (nibbling) for target filter management

NASA Astrophysics Data System (ADS)

Caulfield, H. John; Johnson, John L.

1999-07-01

A new method of classifying objects is presented. Rather than trying to form the classifier in one step or in one training algorithm, it is done in a series of small steps, or nibbles. This leads to an efficient and versatile system that is trained in series with single one-shot examples but applied in parallel, is implemented with single layer perceptrons, yet maintains its fully sequential hierarchical structure. Based on the nibbling algorithm, a basic new method of target reference filter management is described.

Synthesizing genetic sequential logic circuit with clock pulse generator.

PubMed

Chuang, Chia-Hua; Lin, Chun-Liang

2014-05-28

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

Causal Models for Mediation Analysis: An Introduction to Structural Mean Models.

PubMed

Zheng, Cheng; Atkins, David C; Zhou, Xiao-Hua; Rhew, Isaac C

2015-01-01

Mediation analyses are critical to understanding why behavioral interventions work. To yield a causal interpretation, common mediation approaches must make an assumption of "sequential ignorability." The current article describes an alternative approach to causal mediation called structural mean models (SMMs). A specific SMM called a rank-preserving model (RPM) is introduced in the context of an applied example. Particular attention is given to the assumptions of both approaches to mediation. Applying both mediation approaches to the college student drinking data yield notable differences in the magnitude of effects. Simulated examples reveal instances in which the traditional approach can yield strongly biased results, whereas the RPM approach remains unbiased in these cases. At the same time, the RPM approach has its own assumptions that must be met for correct inference, such as the existence of a covariate that strongly moderates the effect of the intervention on the mediator and no unmeasured confounders that also serve as a moderator of the effect of the intervention or the mediator on the outcome. The RPM approach to mediation offers an alternative way to perform mediation analysis when there may be unmeasured confounders.

Microfluidic Device for Sequential Injection and Flushing of Solutions and its Application to Immunosensing

NASA Astrophysics Data System (ADS)

Nashida, Norihiro; Suzuki, Hiroaki

A microfluidic system with injecting and flushing functions was developed. In the system, hydrophilic flow channels have a dry-film photoresist layer which facilitates the introduction of solutions from four injection ports. The injection and flushing of solutions are controlled by valves operated by electrowetting. The valves consist of gold working electrodes in the flow channels or a through-hole in the glass substrate. Solutions can be sequentially introduced through the injection ports into a reaction chamber and flushed through a valve in the through-hole. Necessary immunoassay steps can be conducted on the chip, and a target antibody can be detected electrochemically.

Resolution of concerted versus sequential mechanisms in photo-induced double-proton transfer reaction in 7-azaindole H-bonded dimer

PubMed Central

Catalán, Javier; del Valle, Juan Carlos; Kasha, Michael

1999-01-01

The experimental and theoretical bases for a synchronous or concerted double-proton transfer in centro-symmetric H-bonded electronically excited molecular dimers are presented. The prototype model is the 7-azaindole dimer. New research offers confirmation of a concerted mechanism for excited-state biprotonic transfer. Recent femtosecond photoionization and coulombic explosion techniques have given rise to time-of-flight MS observations suggesting sequential two-step biprotonic transfer for the same dimer. We interpret the overall species observed in the time-of-flight experiments as explicable without conflict with the concerted mechanism of proton transfer. PMID:10411876

Sequential steps of macroautophagy and chaperone-mediated autophagy are involved in the irreversible process of posterior silk gland histolysis during metamorphosis of Bombyx mori.

PubMed

Shiba, Hajime; Yabu, Takeshi; Sudayama, Makoto; Mano, Nobuhiro; Arai, Naoto; Nakanishi, Teruyuki; Hosono, Kuniaki

2016-04-15

To elucidate the degradation process of the posterior silk gland during metamorphosis of the silkworm ITALIC! Bombyx mori, tissues collected on the 6th day after entering the 5th instar (V6), prior to spinning (PS), during spinning (SP) and after cocoon formation (CO) were used to analyze macroautophagy, chaperone-mediated autophagy (CMA) and the adenosine triphosphate (ATP)-dependent ubiquitin proteasome. Immediately after entering metamorphosis stage PS, the levels of ATP and phosphorylated p70S6 kinase protein decreased spontaneously and continued to decline at SP, followed by a notable restoration at CO. In contrast, phosphorylated AMP-activated protein kinase α (AMPKα) showed increases at SP and CO. Most of the Atg8 protein was converted to form II at all stages. The levels of ubiquitinated proteins were high at SP and CO, and low at PS. The proteasome activity was high at V6 and PS but low at SP and CO. In the isolated lysosome fractions, levels of Hsc70/Hsp70 protein began to increase at PS and continued to rise at SP and CO. The lysosomal cathepsin B/L activity showed a dramatic increase at CO. Our results clearly demonstrate that macroautophagy occurs before entering the metamorphosis stage and strongly suggest that the CMA pathway may play an important role in the histolysis of the posterior silk gland during metamorphosis. © 2016. Published by The Company of Biologists Ltd.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets.

PubMed

Seok, Youngung; Joung, Hyou-Arm; Byun, Ju-Young; Jeon, Hyo-Sung; Shin, Su Jeong; Kim, Sanghyo; Shin, Young-Beom; Han, Hyung Soo; Kim, Min-Gon

2017-01-01

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 10 2 -10 5 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets

PubMed Central

Seok, Youngung; Joung, Hyou-Arm; Byun, Ju-Young; Jeon, Hyo-Sung; Shin, Su Jeong; Kim, Sanghyo; Shin, Young-Beom; Han, Hyung Soo; Kim, Min-Gon

2017-01-01

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 102-105 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing. PMID:28740546

Nucleocytoplasmic Transport of RNAs and RNA-Protein Complexes.

PubMed

Sloan, Katherine E; Gleizes, Pierre-Emmanuel; Bohnsack, Markus T

2016-05-22

RNAs and ribonucleoprotein complexes (RNPs) play key roles in mediating and regulating gene expression. In eukaryotes, most RNAs are transcribed, processed and assembled with proteins in the nucleus and then either function in the cytoplasm or also undergo a cytoplasmic phase in their biogenesis. This compartmentalization ensures that sequential steps in gene expression and RNP production are performed in the correct order and it allows important quality control mechanisms that prevent the involvement of aberrant RNAs/RNPs in these cellular pathways. The selective exchange of RNAs/RNPs between the nucleus and cytoplasm is enabled by nuclear pore complexes, which function as gateways between these compartments. RNA/RNP transport is facilitated by a range of nuclear transport receptors and adaptors, which are specifically recruited to their cargos and mediate interactions with nucleoporins to allow directional translocation through nuclear pore complexes. While some transport factors are only responsible for the export/import of a certain class of RNA/RNP, others are multifunctional and, in the case of large RNPs, several export factors appear to work together to bring about export. Recent structural studies have revealed aspects of the mechanisms employed by transport receptors to enable specific cargo recognition, and genome-wide approaches have provided the first insights into the diverse composition of pre-mRNPs during export. Furthermore, the regulation of RNA/RNP export is emerging as an important means to modulate gene expression under stress conditions and in disease. Copyright © 2015. Published by Elsevier Ltd.

A Novel Epigenetic Silencing Pathway Involving the Highly Conserved 5’-3’ Exoribonuclease Dhp1/Rat1/Xrn2 in Schizosaccharomyces pombe

PubMed Central

Tucker, James Franklin; Ohle, Corina; Schermann, Géza; Bendrin, Katja; Zhang, Wei; Fischer, Tamás; Zhang, Ke

2016-01-01

Epigenetic gene silencing plays a critical role in regulating gene expression and contributes to organismal development and cell fate acquisition in eukaryotes. In fission yeast, Schizosaccharomyces pombe, heterochromatin-associated gene silencing is known to be mediated by RNA processing pathways including RNA interference (RNAi) and a 3’-5’ exoribonuclease complex, the exosome. Here, we report a new RNA-processing pathway that contributes to epigenetic gene silencing and assembly of heterochromatin mediated by 5’-3’ exoribonuclease Dhp1/Rat1/Xrn2. Dhp1 mutation causes defective gene silencing both at peri-centromeric regions and at the silent mating type locus. Intriguingly, mutation in either of the two well-characterized Dhp1-interacting proteins, the Din1 pyrophosphohydrolase or the Rhn1 transcription termination factor, does not result in silencing defects at the main heterochromatic regions. We demonstrate that Dhp1 interacts with heterochromatic factors and is essential in the sequential steps of establishing silencing in a manner independent of both RNAi and the exosome. Genomic and genetic analyses suggest that Dhp1 is involved in post-transcriptional silencing of repetitive regions through its RNA processing activity. The results describe the unexpected role of Dhp1/Rat1/Xrn2 in chromatin-based silencing and elucidate how various RNA-processing pathways, acting together or independently, contribute to epigenetic regulation of the eukaryotic genome. PMID:26889830

iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM

PubMed Central

Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen; Powell, Harold R.; Leslie, Andrew G. W.

2011-01-01

iMOSFLM is a graphical user interface to the diffraction data-integration program MOSFLM. It is designed to simplify data processing by dividing the process into a series of steps, which are normally carried out sequentially. Each step has its own display pane, allowing control over parameters that influence that step and providing graphical feedback to the user. Suitable values for integration parameters are set automatically, but additional menus provide a detailed level of control for experienced users. The image display and the interfaces to the different tasks (indexing, strategy calculation, cell refinement, integration and history) are described. The most important parameters for each step and the best way of assessing success or failure are discussed. PMID:21460445

Impaired Response Selection During Stepping Predicts Falls in Older People-A Cohort Study.

PubMed

Schoene, Daniel; Delbaere, Kim; Lord, Stephen R

2017-08-01

Response inhibition, an important executive function, has been identified as a risk factor for falls in older people. This study investigated whether step tests that include different levels of response inhibition differ in their ability to predict falls and whether such associations are mediated by measures of attention, speed, and/or balance. A cohort study with a 12-month follow-up was conducted in community-dwelling older people without major cognitive and mobility impairments. Participants underwent 3 step tests: (1) choice stepping reaction time (CSRT) requiring rapid decision making and step initiation; (2) inhibitory choice stepping reaction time (iCSRT) requiring additional response inhibition and response-selection (go/no-go); and (3) a Stroop Stepping Test (SST) under congruent and incongruent conditions requiring conflict resolution. Participants also completed tests of processing speed, balance, and attention as potential mediators. Ninety-three of the 212 participants (44%) fell in the follow-up period. Of the step tests, only components of the iCSRT task predicted falls in this time with the relative risk per standard deviation for the reaction time (iCSRT-RT) = 1.23 (95%CI = 1.10-1.37). Multiple mediation analysis indicated that the iCSRT-RT was independently associated with falls and not mediated through slow processing speed, poor balance, or inattention. Combined stepping and response inhibition as measured in a go/no-go test stepping paradigm predicted falls in older people. This suggests that integrity of the response-selection component of a voluntary stepping response is crucial for minimizing fall risk. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Design and fabrication of a chitosan hydrogel with gradient structures via a step-by-step cross-linking process.

PubMed

Xu, Yongxiang; Yuan, Shenpo; Han, Jianmin; Lin, Hong; Zhang, Xuehui

2017-11-15

The development of scaffolds to mimic the gradient structure of natural tissue is an important consideration for effective tissue engineering. In the present study, a physical cross-linking chitosan hydrogel with gradient structures was fabricated via a step-by-step cross-linking process using sodium tripolyphosphate and sodium hydroxide as sequential cross-linkers. Chitosan hydrogels with different structures (single, double, and triple layers) were prepared by modifying the gelling process. The properties of the hydrogels were further adjusted by varying the gelling conditions, such as gelling time, pH, and composition of the crosslinking solution. Slight cytotoxicity was showed in MTT assay for hydrogels with uncross-linking chitosan solution and non-cytotoxicity was showed for other hydrogels. The results suggest that step-by-step cross-linking represents a practicable method to fabricate scaffolds with gradient structures. Copyright © 2017. Published by Elsevier Ltd.

Sequential EMT-MET induces neuronal conversion through Sox2

PubMed Central

He, Songwei; Chen, Jinlong; Zhang, Yixin; Zhang, Mengdan; Yang, Xiao; Li, Yuan; Sun, Hao; Lin, Lilong; Fan, Ke; Liang, Lining; Feng, Chengqian; Wang, Fuhui; Zhang, Xiao; Guo, Yiping; Pei, Duanqing; Zheng, Hui

2017-01-01

Direct neuronal conversion can be achieved with combinations of small-molecule compounds and growth factors. Here, by studying the first or induction phase of the neuronal conversion induced by defined 5C medium, we show that the Sox2-mediated switch from early epithelial–mesenchymal transition (EMT) to late mesenchymal–epithelial transition (MET) within a high proliferation context is essential and sufficient for the conversion from mouse embryonic fibroblasts (MEFs) to TuJ+ cells. At the early stage, insulin and basic fibroblast growth factor (bFGF)-induced cell proliferation, early EMT, the up-regulation of Stat3 and Sox2, and the subsequent activation of neuron projection. Up-regulated Sox2 then induced MET and directed cells towards a neuronal fate at the late stage. Inhibiting either stage of this sequential EMT-MET impaired the conversion. In addition, Sox2 could replace sequential EMT-MET to induce a similar conversion within a high proliferation context, and its functions were confirmed with other neuronal conversion protocols and MEFs reprogramming. Therefore, the critical roles of the sequential EMT-MET were implicated in direct cell fate conversion in addition to reprogramming, embryonic development and cancer progression. PMID:28580167

78 FR 72571 - Extension of Expiration Date for Mental Disorders Body System Listings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-03

... of Expiration Date for Mental Disorders Body System Listings AGENCY: Social Security Administration. ACTION: Final rule. SUMMARY: We are extending the expiration date of the Mental Disorders body system in... need to evaluate mental disorders at step three of the sequential evaluation processes for initial...

Systematic assessment of benefits and risks: study protocol for a multi-criteria decision analysis using the Analytic Hierarchy Process for comparative effectiveness research

PubMed Central

Singh, Sonal

2013-01-01

Background: Regulatory decision-making involves assessment of risks and benefits of medications at the time of approval or when relevant safety concerns arise with a medication. The Analytic Hierarchy Process (AHP) facilitates decision-making in complex situations involving tradeoffs by considering risks and benefits of alternatives. The AHP allows a more structured method of synthesizing and understanding evidence in the context of importance assigned to outcomes. Our objective is to evaluate the use of an AHP in a simulated committee setting selecting oral medications for type 2 diabetes.  Methods: This study protocol describes the AHP in five sequential steps using a small group of diabetes experts representing various clinical disciplines. The first step will involve defining the goal of the decision and developing the AHP model. In the next step, we will collect information about how well alternatives are expected to fulfill the decision criteria. In the third step, we will compare the ability of the alternatives to fulfill the criteria and judge the importance of eight criteria relative to the decision goal of the optimal medication choice for type 2 diabetes. We will use pairwise comparisons to sequentially compare the pairs of alternative options regarding their ability to fulfill the criteria. In the fourth step, the scales created in the third step will be combined to create a summary score indicating how well the alternatives met the decision goal. The resulting scores will be expressed as percentages and will indicate the alternative medications' relative abilities to fulfill the decision goal. The fifth step will consist of sensitivity analyses to explore the effects of changing the estimates. We will also conduct a cognitive interview and process evaluation.  Discussion: Multi-criteria decision analysis using the AHP will aid, support and enhance the ability of decision makers to make evidence-based informed decisions consistent with their values and preferences. PMID:24555077

Systematic assessment of benefits and risks: study protocol for a multi-criteria decision analysis using the Analytic Hierarchy Process for comparative effectiveness research.

PubMed

Maruthur, Nisa M; Joy, Susan; Dolan, James; Segal, Jodi B; Shihab, Hasan M; Singh, Sonal

2013-01-01

Regulatory decision-making involves assessment of risks and benefits of medications at the time of approval or when relevant safety concerns arise with a medication. The Analytic Hierarchy Process (AHP) facilitates decision-making in complex situations involving tradeoffs by considering risks and benefits of alternatives. The AHP allows a more structured method of synthesizing and understanding evidence in the context of importance assigned to outcomes. Our objective is to evaluate the use of an AHP in a simulated committee setting selecting oral medications for type 2 diabetes.  This study protocol describes the AHP in five sequential steps using a small group of diabetes experts representing various clinical disciplines. The first step will involve defining the goal of the decision and developing the AHP model. In the next step, we will collect information about how well alternatives are expected to fulfill the decision criteria. In the third step, we will compare the ability of the alternatives to fulfill the criteria and judge the importance of eight criteria relative to the decision goal of the optimal medication choice for type 2 diabetes. We will use pairwise comparisons to sequentially compare the pairs of alternative options regarding their ability to fulfill the criteria. In the fourth step, the scales created in the third step will be combined to create a summary score indicating how well the alternatives met the decision goal. The resulting scores will be expressed as percentages and will indicate the alternative medications' relative abilities to fulfill the decision goal. The fifth step will consist of sensitivity analyses to explore the effects of changing the estimates. We will also conduct a cognitive interview and process evaluation.  Multi-criteria decision analysis using the AHP will aid, support and enhance the ability of decision makers to make evidence-based informed decisions consistent with their values and preferences.

Lignin oxidation and pulp delignification by laccase and mediators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourbonnais, R.; Paice, M.G.; Reid, I.D.

1996-10-01

The phenol oxidizing enzyme laccase is produced abundantly by the lignin-degrading fungus Trametes versicolor. We found previously that laccase can oxidize veratryl alcohol and other non-phenolic lignin model compounds when a mediator such as 2,2{prime}-azinobis(3-ethylbenzthiazoline-5-sulphonate) (ABTS) was present. The laccase/mediator couple was also shown to be effective for delignification of kraft pulps. Two different isozymes of laccase produced by this fungus were purified and their reactivities towards lignins and kraft pulps were studied. The mediator ABTS was shown to be essential for pulp delignification and to reverse the polymerization of kraft lignin by either laccase. Pulp delignification with laccase andmore » ABTS was also optimized. resulting in up to 55% lignin removal from kraft pulp following sequential enzyme treatments and alkaline extractions. Several variables were surveyed including enzyme and mediator dosage, oxygen pressure, temperature, reaction time, and pH.« less

Anxiety and Self-Efficacy as Sequential Mediators in US College Students' Career Preparation

ERIC Educational Resources Information Center

Deer, LillyBelle K.; Gohn, Kelsey; Kanaya, Tomoe

2018-01-01

Purpose: Current college students in the USA are reporting higher levels of anxiety over career planning than previous generations, placing pressure on colleges to provide effective career development opportunities for their students. Research has consistently found that increasing career-related self-efficacy is particularly effective at…

Hierarchical Modeling of Sequential Behavioral Data: Examining Complex Association Patterns in Mediation Models

ERIC Educational Resources Information Center

Dagne, Getachew A.; Brown, C. Hendricks; Howe, George W.

2007-01-01

This article presents new methods for modeling the strength of association between multiple behaviors in a behavioral sequence, particularly those involving substantively important interaction patterns. Modeling and identifying such interaction patterns becomes more complex when behaviors are assigned to more than two categories, as is the case…

If Only my Leader Would just Do Something! Passive Leadership Undermines Employee Well-being Through Role Stressors and Psychological Resource Depletion.

PubMed

Barling, Julian; Frone, Michael R

2017-08-01

The goal of this study was to develop and test a sequential mediational model explaining the negative relationship of passive leadership to employee well-being. Based on role stress theory, we posit that passive leadership will predict higher levels of role ambiguity, role conflict and role overload. Invoking Conservation of Resources theory, we further hypothesize that these role stressors will indirectly and negatively influence two aspects of employee well-being, namely overall mental health and overall work attitude, through psychological work fatigue. Using a probability sample of 2467 US workers, structural equation modelling supported the model by showing that role stressors and psychological work fatigue partially mediated the negative relationship between passive leadership and both aspects of employee well-being. The hypothesized, sequential indirect relationships explained 47.9% of the overall relationship between passive leadership and mental health and 26.6% of the overall relationship between passive leadership and overall work attitude. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Unusual behavior in magnesium-copper cluster matter produced by helium droplet mediated deposition.

PubMed

Emery, S B; Xin, Y; Ridge, C J; Buszek, R J; Boatz, J A; Boyle, J M; Little, B K; Lindsay, C M

2015-02-28

We demonstrate the ability to produce core-shell nanoclusters of materials that typically undergo intermetallic reactions using helium droplet mediated deposition. Composite structures of magnesium and copper were produced by sequential condensation of metal vapors inside the 0.4 K helium droplet baths and then gently deposited onto a substrate for analysis. Upon deposition, the individual clusters, with diameters ∼5 nm, form a cluster material which was subsequently characterized using scanning and transmission electron microscopies. Results of this analysis reveal the following about the deposited cluster material: it is in the un-alloyed chemical state, it maintains a stable core-shell 5 nm structure at sub-monolayer quantities, and it aggregates into unreacted structures of ∼75 nm during further deposition. Surprisingly, high angle annular dark field scanning transmission electron microscopy images revealed that the copper appears to displace the magnesium at the core of the composite cluster despite magnesium being the initially condensed species within the droplet. This phenomenon was studied further using preliminary density functional theory which revealed that copper atoms, when added sequentially to magnesium clusters, penetrate into the magnesium cores.

Sequential and coordinated action of phytochromes A and B during Arabidopsis stem growth revealed by kinetic analysis

NASA Technical Reports Server (NTRS)

Parks, B. M.; Spalding, E. P.; Evans, M. L. (Principal Investigator)

1999-01-01

Photoreceptor proteins of the phytochrome family mediate light-induced inhibition of stem (hypocotyl) elongation during the development of photoautotrophy in seedlings. Analyses of overt mutant phenotypes have established the importance of phytochromes A and B (phyA and phyB) in this developmental process, but kinetic information that would augment emerging molecular models of phytochrome signal transduction is absent. We have addressed this deficiency by genetically dissecting phytochrome-response kinetics, after having solved the technical issues that previously limited growth studies of small Arabidopsis seedlings. We show here, with resolution on the order of minutes, that phyA initiated hypocotyl growth inhibition upon the onset of continuous red light. This primary contribution of phyA began to decrease after 3 hr of irradiation, the same time at which immunochemically detectable phyA disappeared and an exclusively phyB-dependent phase of inhibition began. The sequential and coordinated actions of phyA and phyB in red light were not observed in far-red light, which inhibited growth persistently through an exclusively phyA-mediated pathway.

UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-β1-FAP-α.

PubMed

Wäster, Petra; Orfanidis, Kyriakos; Eriksson, Ida; Rosdahl, Inger; Seifert, Oliver; Öllinger, Karin

2017-08-08

Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-α is not yet completely revealed. Expression of FAP-α was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-β1. Fibroblast activation protein-α expression was induced by UVR in melanocytes of human skin. The FAP-α expression was regulated by UVR-induced release of TGF-β1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-α mediated ECM degradation and facilitated tumour cell dissemination. Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-β1 and FAP-α expression, promoting cancer cell dissemination and melanoma metastatic spread.

PC_Eyewitness: evaluating the New Jersey method.

PubMed

MacLin, Otto H; Phelan, Colin M

2007-05-01

One important variable in eyewitness identification research is lineup administration procedure. Lineups administered sequentially (one at a time) have been shown to reduce the number of false identifications in comparison with those administered simultaneously (all at once). As a result, some policymakers have adopted sequential administration. However, they have made slight changes to the method used in psychology laboratories. Eyewitnesses in the field are allowed to take multiple passes through a lineup, whereas participants in the laboratory are allowed only one pass. PC_Eyewitness (PCE) is a computerized system used to construct and administer simultaneous or sequential lineups in both the laboratory and the field. It is currently being used in laboratories investigating eyewitness identification in the United States, Canada, and abroad. A modified version of PCE is also being developed for a local police department. We developed a new module for PCE, the New Jersey module, to examine the effects of a second pass. We found that the sequential advantage was eliminated when the participants were allowed to view the lineup a second time. The New Jersey module, and steps we are taking to improve on the module, are presented here and are being made available to the research and law enforcement communities.

Determination of ambroxol hydrochloride, methylparaben and benzoic acid in pharmaceutical preparations based on sequential injection technique coupled with monolithic column.

PubMed

Satínský, Dalibor; Huclová, Jitka; Ferreira, Raquel L C; Montenegro, Maria Conceição B S M; Solich, Petr

2006-02-13

The porous monolithic columns show high performance at relatively low pressure. The coupling of short monoliths with sequential injection technique (SIA) results in a new approach to implementation of separation step to non-separation low-pressure method. In this contribution, a new separation method for simultaneous determination of ambroxol, methylparaben and benzoic acid was developed based on a novel reversed-phase sequential injection chromatography (SIC) technique with UV detection. A Chromolith SpeedROD RP-18e, 50-4.6 mm column with 10 mm precolumn and a FIAlab 3000 system with a six-port selection valve and 5 ml syringe were used for sequential injection chromatographic separations in our study. The mobile phase used was acetonitrile-tetrahydrofuran-0.05M acetic acid (10:10:90, v/v/v), pH 3.75 adjusted with triethylamine, flow rate 0.48 mlmin(-1), UV-detection was at 245 nm. The analysis time was <11 min. A new SIC method was validated and compared with HPLC. The method was found to be useful for the routine analysis of the active compounds ambroxol and preservatives (methylparaben or benzoic acid) in various pharmaceutical syrups and drops.

45 CFR 16.18 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 16.18 Section 16.18 Public Welfare... BOARD § 16.18 Mediation. (a) In cases pending before the Board. If the Board decides that mediation... mediation techniques and will provide or assist in selecting a mediator. The mediator may take any steps...

12-step affiliation and attendance following treatment for comorbid substance dependence and depression: a latent growth curve mediation model.

PubMed

Worley, Matthew J; Tate, Susan R; McQuaid, John R; Granholm, Eric L; Brown, Sandra A

2013-01-01

Among substance-dependent individuals, comorbid major depressive disorder (MDD) is associated with greater severity and poorer treatment outcomes, but little research has examined mediators of posttreatment substance use outcomes within this population. Using latent growth curve models, the authors tested relationships between individual rates of change in 12-step involvement and substance use, utilizing posttreatment follow-up data from a trial of group Twelve-Step Facilitation (TSF) and integrated cognitive-behavioral therapy (ICBT) for veterans with substance dependence and MDD. Although TSF patients were higher on 12-step affiliation and meeting attendance at end-of-treatment as compared with ICBT, they also experienced significantly greater reductions in these variables during the year following treatment, ending at similar levels as ICBT. Veterans in TSF also had significantly greater increases in drinking frequency during follow-up, and this group difference was mediated by their greater reductions in 12-step affiliation and meeting attendance. Patients with comorbid depression appear to have difficulty sustaining high levels of 12-step involvement after the conclusion of formal 12-step interventions, which predicts poorer drinking outcomes over time. Modifications to TSF and other formal 12-step protocols or continued therapeutic contact may be necessary to sustain 12-step involvement and reduced drinking for patients with substance dependence and MDD.

Synthesizing genetic sequential logic circuit with clock pulse generator

PubMed Central

2014-01-01

Background Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. Results This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. Conclusions A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal. PMID:24884665

Interrole conflict and self-efficacy to manage work and family demands mediate the relationships of job and family demands with stress in the job and family domains.

PubMed

Smoktunowicz, Ewelina; Cieslak, Roman; Demerouti, Evangelia

2017-09-01

This study derives from Work-Home Resources model (ten Brummelhuis, L. L., & Bakker, A. B. (2012). A resource perspective on the work-home interface: The work-home resources model. American Psychologist, 67(7), 545-556. doi: 10.1037/a0027974 ) and Social Cognitive Theory (Bandura, A. (1986). Social foundations of thought and action: A social cognitive theory. Englewood Cliffs, NJ, US: Prentice-Hall, Inc.) to investigate mechanisms responsible for the effect of job and family demands on work- and family-related perceived stress. We hypothesized that interrole conflict and self-efficacy to manage work and family demands operate either independently or sequentially transmitting the effects of demands on perceived stress. A sample of 100 employees of various occupations participated in the study conducted online in two waves: Time 1 (T1) and Time 2 (T2) with a three-month interval. Regression analysis with bootstrapping was applied. Interrole conflict (T1) did not mediate the relationships between demands (T1) and perceived stress (T2), whereas self-efficacy (T1) mediated only those between family demands (T1) and stress (T2). However, data supported the sequential mediation hypotheses: Demands (T1) were associated with increased interrole conflict (T1) which in turn decreased self-efficacy (T1) and ultimately resulted in the elevated perceived stress at work and in the family (T2). Demands originating in one domain can impact stress both in the same and other life areas through the sequence of interrole conflict and context-specific self-efficacy.

Full Intelligent Cancer Classification of Thermal Breast Images to Assist Physician in Clinical Diagnostic Applications

PubMed Central

Lashkari, AmirEhsan; Pak, Fatemeh; Firouzmand, Mohammad

2016-01-01

Breast cancer is the most common type of cancer among women. The important key to treat the breast cancer is early detection of it because according to many pathological studies more than 75% – 80% of all abnormalities are still benign at primary stages; so in recent years, many studies and extensive research done to early detection of breast cancer with higher precision and accuracy. Infra-red breast thermography is an imaging technique based on recording temperature distribution patterns of breast tissue. Compared with breast mammography technique, thermography is more suitable technique because it is noninvasive, non-contact, passive and free ionizing radiation. In this paper, a full automatic high accuracy technique for classification of suspicious areas in thermogram images with the aim of assisting physicians in early detection of breast cancer has been presented. Proposed algorithm consists of four main steps: pre-processing & segmentation, feature extraction, feature selection and classification. At the first step, using full automatic operation, region of interest (ROI) determined and the quality of image improved. Using thresholding and edge detection techniques, both right and left breasts separated from each other. Then relative suspected areas become segmented and image matrix normalized due to the uniqueness of each person's body temperature. At feature extraction stage, 23 features, including statistical, morphological, frequency domain, histogram and Gray Level Co-occurrence Matrix (GLCM) based features are extracted from segmented right and left breast obtained from step 1. To achieve the best features, feature selection methods such as minimum Redundancy and Maximum Relevance (mRMR), Sequential Forward Selection (SFS), Sequential Backward Selection (SBS), Sequential Floating Forward Selection (SFFS), Sequential Floating Backward Selection (SFBS) and Genetic Algorithm (GA) have been used at step 3. Finally to classify and TH labeling procedures, different classifiers such as AdaBoost, Support Vector Machine (SVM), k-Nearest Neighbors (kNN), Naïve Bayes (NB) and probability Neural Network (PNN) are assessed to find the best suitable one. These steps are applied on different thermogram images degrees. The results obtained on native database showed the best and significant performance of the proposed algorithm in comprise to the similar studies. According to experimental results, GA combined with AdaBoost with the mean accuracy of 85.33% and 87.42% on the left and right breast images with 0 degree, GA combined with AdaBoost with mean accuracy of 85.17% on the left breast images with 45 degree and mRMR combined with AdaBoost with mean accuracy of 85.15% on the right breast images with 45 degree, and also GA combined with AdaBoost with a mean accuracy of 84.67% and 86.21%, on the left and right breast images with 90 degree, are the best combinations of feature selection and classifier for evaluation of breast images. PMID:27014608

Robust multiperson detection and tracking for mobile service and social robots.

PubMed

Li, Liyuan; Yan, Shuicheng; Yu, Xinguo; Tan, Yeow Kee; Li, Haizhou

2012-10-01

This paper proposes an efficient system which integrates multiple vision models for robust multiperson detection and tracking for mobile service and social robots in public environments. The core technique is a novel maximum likelihood (ML)-based algorithm which combines the multimodel detections in mean-shift tracking. First, a likelihood probability which integrates detections and similarity to local appearance is defined. Then, an expectation-maximization (EM)-like mean-shift algorithm is derived under the ML framework. In each iteration, the E-step estimates the associations to the detections, and the M-step locates the new position according to the ML criterion. To be robust to the complex crowded scenarios for multiperson tracking, an improved sequential strategy to perform the mean-shift tracking is proposed. Under this strategy, human objects are tracked sequentially according to their priority order. To balance the efficiency and robustness for real-time performance, at each stage, the first two objects from the list of the priority order are tested, and the one with the higher score is selected. The proposed method has been successfully implemented on real-world service and social robots. The vision system integrates stereo-based and histograms-of-oriented-gradients-based human detections, occlusion reasoning, and sequential mean-shift tracking. Various examples to show the advantages and robustness of the proposed system for multiperson tracking from mobile robots are presented. Quantitative evaluations on the performance of multiperson tracking are also performed. Experimental results indicate that significant improvements have been achieved by using the proposed method.

II. Inhibited Diffusion Driven Surface Transmutations

NASA Astrophysics Data System (ADS)

Chubb, Talbot A.

2006-02-01

This paper is the second of a set of three papers dealing with the role of coherent partitioning as a common element in Low Energy Nuclear Reactions (LENR), by which is meant cold-fusion related processes. This paper discusses the first step in a sequence of four steps that seem to be necessary to explain Iwamura 2-α-addition surface transmutations. Three concepts are examined: salt-metal interface states, sequential tunneling that transitions D+ ions from localized interstitial to Bloch form, and the general applicability of 2-dimensional vs. 3-dimensional symmetry hosting networks.

Recursive Directional Ligation Approach for Cloning Recombinant Spider Silks.

PubMed

Dinjaski, Nina; Huang, Wenwen; Kaplan, David L

2018-01-01

Recent advances in genetic engineering have provided a route to produce various types of recombinant spider silks. Different cloning strategies have been applied to achieve this goal (e.g., concatemerization, step-by-step ligation, recursive directional ligation). Here we describe recursive directional ligation as an approach that allows for facile modularity and control over the size of the genetic cassettes. This approach is based on sequential ligation of genetic cassettes (monomers) where the junctions between them are formed without interrupting key gene sequences with additional base pairs.

Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling

PubMed Central

Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

2013-01-01

Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways. PMID:23764850

Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling.

PubMed

Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

2013-06-13

Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways.

The Effect of Social Support on Glycemic Control in Patients with Type 2 Diabetes Mellitus: The Mediating Roles of Self-Efficacy and Adherence

PubMed Central

Shao, Yechang; Liang, Lu; Shi, Linjing; Yu, Shouyi

2017-01-01

Ample evidence suggests that social support, self-efficacy, and adherence significantly, independently, and together affect glycemic control in patients with type 2 diabetes mellitus (T2DM), but the pathway from social support to glycemic control remains unclear. This study hypothesized that the effect of social support on glycemic control was mediated sequentially by self-efficacy and adherence. Patients with T2DM were recruited from two hospitals in Guangzhou, China, from January 1 to July 31, 2014, and their sociodemographic clinical data and their assessments on social support, self-efficacy, and adherence were obtained from medical records and self-completed questionnaires. Of the 532 patients who participated, 35% achieved glycemic control (i.e., HbA1c < 7%). Social support, self-efficacy, and adherence had significant correlations with each other and with glycemic control (P < 0.05). Regression analyses and structural equation modeling showed that better social support was associated to better patient self-efficacy, which, in turn, was associated with better medical adherence, which was associated with improved glycemic control, and the relationship between social support and glycemic control was sequentially and completely mediated by self-efficacy and adherence. The five goodness-of-fit indices confirmed that our data fitted the hypothesized pathway model strongly. PMID:28626769

Paper-based microfluidics with an erodible polymeric bridge giving controlled release and timed flow shutoff.

PubMed

Jahanshahi-Anbuhi, Sana; Henry, Aleah; Leung, Vincent; Sicard, Clémence; Pennings, Kevin; Pelton, Robert; Brennan, John D; Filipe, Carlos D M

2014-01-07

Water soluble pullulan films were formatted into paper-based microfluidic devices, serving as a controlled time shutoff valve. The utility of the valve was demonstrated by a one-step, fully automatic implementation of a complex pesticide assay requiring timed, sequential exposure of an immobilized enzyme layer to separate liquid streams. Pullulan film dissolution and the capillary wicking of aqueous solutions through the device were measured and modeled providing valve design criteria. The films dissolve mainly by surface erosion, meaning the film thickness mainly controls the shutoff time. This method can also provide time-dependent sequential release of reagents without compromising the simplicity and low cost of paper-based devices.

Causal mediation analysis with a latent mediator.

PubMed

Albert, Jeffrey M; Geng, Cuiyu; Nelson, Suchitra

2016-05-01

Health researchers are often interested in assessing the direct effect of a treatment or exposure on an outcome variable, as well as its indirect (or mediation) effect through an intermediate variable (or mediator). For an outcome following a nonlinear model, the mediation formula may be used to estimate causally interpretable mediation effects. This method, like others, assumes that the mediator is observed. However, as is common in structural equations modeling, we may wish to consider a latent (unobserved) mediator. We follow a potential outcomes framework and assume a generalized structural equations model (GSEM). We provide maximum-likelihood estimation of GSEM parameters using an approximate Monte Carlo EM algorithm, coupled with a mediation formula approach to estimate natural direct and indirect effects. The method relies on an untestable sequential ignorability assumption; we assess robustness to this assumption by adapting a recently proposed method for sensitivity analysis. Simulation studies show good properties of the proposed estimators in plausible scenarios. Our method is applied to a study of the effect of mother education on occurrence of adolescent dental caries, in which we examine possible mediation through latent oral health behavior. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developing and Implementing a Framework of Participatory Simulation for Mobile Learning Using Scaffolding

ERIC Educational Resources Information Center

Yin, Chengjiu; Song, Yanjie; Tabata, Yoshiyuki; Ogata, Hiroaki; Hwang, Gwo-Jen

2013-01-01

This paper proposes a conceptual framework, scaffolding participatory simulation for mobile learning (SPSML), used on mobile devices for helping students learn conceptual knowledge in the classroom. As the pedagogical design, the framework adopts an experiential learning model, which consists of five sequential but cyclic steps: the initial stage,…

Concise total syntheses of (+/-)-strychnine and (+/-)-akuammicine.

PubMed

Sirasani, Gopal; Paul, Tapas; Dougherty, William; Kassel, Scott; Andrade, Rodrigo B

2010-05-21

Concise total syntheses of Strychnos alkaloids strychnine (1) and akuammicine (2) have been realized in 13 and 6 operations, respectively. Key steps include (1) the vinylogous Mannich reaction; (2) a novel, sequential one-pot spirocyclization/intramolecular aza-Baylis-Hillman reaction; and (3) a Heck cyclization. The synthesis of 1 proceeds via the Wieland-Gumlich aldehyde (26).

Neural Correlates of Sequence Learning with Stochastic Feedback

ERIC Educational Resources Information Center

Averbeck, Bruno B.; Kilner, James; Frith, Christopher D.

2011-01-01

Although much is known about decision making under uncertainty when only a single step is required in the decision process, less is known about sequential decision making. We carried out a stochastic sequence learning task in which subjects had to use noisy feedback to learn sequences of button presses. We compared flat and hierarchical behavioral…

A Model for Retraining/Training of Business and Industry Employees.

ERIC Educational Resources Information Center

Portland Community Coll., OR.

This model was developed to assist Oregon community colleges in making a planned response to the needs of business and industry for retraining/training of their employees. The model offers a streamlined process for making needs assessments in business and industry through sequential steps for converting needs data into instructional programs. The…

Non-formal Education in the Philippines: A Fundamental Step towards Lifelong Learning.

ERIC Educational Resources Information Center

Gonzales, Ma. Celeste T.; Pijano, Ma. Concepcion V.

In order to significantly contribute to human resource development, the Philippines must develop an integrated educational system of lifelong learning, with a special emphasis on non-formal education. Despite the value that is placed on formal, or sequential academic schooling, it is non-formal schooling that makes accessible the acquisition of…

School-Based Mutual Support Groups for Parents: An Intervention Guidebook.

ERIC Educational Resources Information Center

Simoni, Jane M.

This handbook focuses on steps and tasks related to establishing mutual support groups for parents in a school setting. A sequential approach is described that involves: working within the school to get started; recruiting members; training parents how to run their own meetings; and offering off-site consultation as requested. The first section…

PROCEDURES FOR THE ESTABLISHMENT OF PUBLIC 2-YEAR COLLEGES.

ERIC Educational Resources Information Center

MORRISON, D.G.; WITHERSPOON, CLINETTE F.

A SURVEY OF EXISTING LEGISLATION, PLANS, AND PROCEDURES FOR ESTABLISHING JUNIOR COLLEGES LED TO THE PREPARATION OF A SET OF SIX SUGGESTED GUIDELINES--(1) NEED FOR ENABLING LEGISLATION, CRITERIA FOR ESTABLISHMENT, AND PROCEDURES FOR ESTABLISHMENT, (2) 15 SEQUENTIAL STEPS, NOT ALL OF WHICH MAY BE NEEDED IN EVERY SITUATION, (3) DEVELOPMENT BY THE…

A Proposed System of "Project Management" for Study Items.

ERIC Educational Resources Information Center

Worcester Public Schools, MA.

The purposes of the proposed system are to provide a standard operating procedure for a systematic and effective handling of project-type study items as differentiated from informational-type items; to assign definite singular responsibility for projects; to suggest specific sequential steps to be taken in the preparation of the project report;…

Behavioral Talk-Write as a Method for Teaching Technical Editing.

ERIC Educational Resources Information Center

Gilbertsen, Michael; Killingsworth, M. Jimmie

1987-01-01

Presents a process-oriented method for teachers of stylistic editing workshops that allows them to (1) focus on individual students, (2) start with students basic repertory of responses and build from there, (3) work with freely emitted behavior, (4) ensure frequent and brief responses, and (5) achieve desired behavior through sequential steps.…

Dynamic Processes at Semiconductor Interfaces: Atomic Intermixing, Diffusion Barriers, and Stability

DTIC Science & Technology

1991-08-15

that the movement of the Fermi level position at the Si surface and the variation of heterojunction band lineup correlated to the density of...that the topmost layer of As atoms was initially involved in a sequential two-step reaction to produce As l - and As 3+- like oxides. These reactions

PATTERN RECOGNITION APPROACH TO MEDICAL DIAGNOSIS,

DTIC Science & Technology

A sequential method of pattern recognition was used to recognize hyperthyroidism in a sample of 2219 patients being treated at the Straub Clinic in...the most prominent class features are selected. Thus, the symptoms which best distinguish hyperthyroidism are extracted at every step and the number of tests required to reach a diagnosis is reduced. (Author)

Catalytic asymmetric synthesis of 2,2-disubstituted oxetanes from ketones by using a one-pot sequential addition of sulfur ylide.

PubMed

Sone, Toshihiko; Lu, Gang; Matsunaga, Shigeki; Shibasaki, Masakatsu

2009-01-01

Better the second time around: The title compounds were synthesized by using a one-pot double methylene transfer catalyzed by a heterobimetallic La/Li complex. Chiral amplification in the second step was the key to obtaining oxetanes in high enantiomeric excess (see scheme).

LabVIEW-based sequential-injection analysis system for the determination of trace metals by square-wave anodic and adsorptive stripping voltammetry on mercury-film electrodes.

PubMed

Economou, Anastasios; Voulgaropoulos, Anastasios

2003-01-01

The development of a dedicated automated sequential-injection analysis apparatus for anodic stripping voltammetry (ASV) and adsorptive stripping voltammetry (AdSV) is reported. The instrument comprised a peristaltic pump, a multiposition selector valve and a home-made potentiostat and used a mercury-film electrode as the working electrodes in a thin-layer electrochemical detector. Programming of the experimental sequence was performed in LabVIEW 5.1. The sequence of operations included formation of the mercury film, electrolytic or adsorptive accumulation of the analyte on the electrode surface, recording of the voltammetric current-potential response, and cleaning of the electrode. The stripping step was carried out by applying a square-wave (SW) potential-time excitation signal to the working electrode. The instrument allowed unattended operation since multiple-step sequences could be readily implemented through the purpose-built software. The utility of the analyser was tested for the determination of copper(II), cadmium(II), lead(II) and zinc(II) by SWASV and of nickel(II), cobalt(II) and uranium(VI) by SWAdSV.

LabVIEW-based sequential-injection analysis system for the determination of trace metals by square-wave anodic and adsorptive stripping voltammetry on mercury-film electrodes

PubMed Central

Economou, Anastasios; Voulgaropoulos, Anastasios

2003-01-01

The development of a dedicated automated sequential-injection analysis apparatus for anodic stripping voltammetry (ASV) and adsorptive stripping voltammetry (AdSV) is reported. The instrument comprised a peristaltic pump, a multiposition selector valve and a home-made potentiostat and used a mercury-film electrode as the working electrodes in a thin-layer electrochemical detector. Programming of the experimental sequence was performed in LabVIEW 5.1. The sequence of operations included formation of the mercury film, electrolytic or adsorptive accumulation of the analyte on the electrode surface, recording of the voltammetric current-potential response, and cleaning of the electrode. The stripping step was carried out by applying a square-wave (SW) potential-time excitation signal to the working electrode. The instrument allowed unattended operation since multiple-step sequences could be readily implemented through the purpose-built software. The utility of the analyser was tested for the determination of copper(II), cadmium(II), lead(II) and zinc(II) by SWASV and of nickel(II), cobalt(II) and uranium(VI) by SWAdSV. PMID:18924623

Comparison between variable and fixed dwell-time PN acquisition algorithms. [for synchronization in pseudonoise spread spectrum systems

NASA Technical Reports Server (NTRS)

Braun, W. R.

1981-01-01

Pseudo noise (PN) spread spectrum systems require a very accurate alignment between the PN code epochs at the transmitter and receiver. This synchronism is typically established through a two-step algorithm, including a coarse synchronization procedure and a fine synchronization procedure. A standard approach for the coarse synchronization is a sequential search over all code phases. The measurement of the power in the filtered signal is used to either accept or reject the code phase under test as the phase of the received PN code. This acquisition strategy, called a single dwell-time system, has been analyzed by Holmes and Chen (1977). A synopsis of the field of sequential analysis as it applies to the PN acquisition problem is provided. From this, the implementation of the variable dwell time algorithm as a sequential probability ratio test is developed. The performance of this algorithm is compared to the optimum detection algorithm and to the fixed dwell-time system.

Sequential ChIP Protocol for Profiling Bivalent Epigenetic Modifications (ReChIP).

PubMed

Desvoyes, Bénédicte; Sequeira-Mendes, Joana; Vergara, Zaida; Madeira, Sofia; Gutierrez, Crisanto

2018-01-01

Identification of chromatin modifications, e.g., histone acetylation and methylation, among others, is widely carried out by using a chromatin immunoprecipitation (ChIP) strategy. The information obtained with these procedures is useful to gain an overall picture of modifications present in all cells of the population under study. It also serves as a basis to figure out the mechanisms of chromatin organization and gene regulation at the population level. However, the ultimate goal is to understand gene regulation at the level of single chromatin fibers. This requires the identification of chromatin modifications that occur at a given genomic location and within the same chromatin fiber. This is achieved by following a sequential ChIP strategy using two antibodies to distinguish different chromatin modifications. Here, we describe a sequential ChIP protocol (Re-ChIP), paying special attention to the controls needed and the required steps to obtain meaningful and reproducible results. The protocol is developed for young Arabidopsis seedlings but could be adapted to other plant materials.

Crystal Growth and Dissolution of Methylammonium Lead Iodide Perovskite in Sequential Deposition: Correlation between Morphology Evolution and Photovoltaic Performance.

PubMed

Hsieh, Tsung-Yu; Huang, Chi-Kai; Su, Tzu-Sen; Hong, Cheng-You; Wei, Tzu-Chien

2017-03-15

Crystal morphology and structure are important for improving the organic-inorganic lead halide perovskite semiconductor property in optoelectronic, electronic, and photovoltaic devices. In particular, crystal growth and dissolution are two major phenomena in determining the morphology of methylammonium lead iodide perovskite in the sequential deposition method for fabricating a perovskite solar cell. In this report, the effect of immersion time in the second step, i.e., methlyammonium iodide immersion in the morphological, structural, optical, and photovoltaic evolution, is extensively investigated. Supported by experimental evidence, a five-staged, time-dependent evolution of the morphology of methylammonium lead iodide perovskite crystals is established and is well connected to the photovoltaic performance. This result is beneficial for engineering optimal time for methylammonium iodide immersion and converging the solar cell performance in the sequential deposition route. Meanwhile, our result suggests that large, well-faceted methylammonium lead iodide perovskite single crystal may be incubated by solution process. This offers a low cost route for synthesizing perovskite single crystal.

Interdisciplinary cognitive task analysis: a strategy to develop a comprehensive endoscopic retrograde cholangiopancreatography protocol for use in fellowship training.

PubMed

Canopy, Erin; Evans, Matt; Boehler, Margaret; Roberts, Nicole; Sanfey, Hilary; Mellinger, John

2015-10-01

Endoscopic retrograde cholangiopancreatography is a challenging procedure performed by surgeons and gastroenterologists. We employed cognitive task analysis to identify steps and decision points for this procedure. Standardized interviews were conducted with expert gastroenterologists (7) and surgeons (4) from 4 institutions. A procedural step and cognitive decision point protocol was created from audio-taped transcriptions and was refined by 5 additional surgeons. Conceptual elements, sequential actions, and decision points were iterated for 5 tasks: patient preparation, duodenal intubation, selective cannulation, imaging interpretation with related therapeutic intervention, and complication management. A total of 180 steps were identified. Gastroenterologists identified 34 steps not identified by surgeons, and surgeons identified 20 steps not identified by gastroenterologists. The findings suggest that for complex procedures performed by diverse practitioners, more experts may help delineate distinctive emphases differentiated by training background and type of practice. Copyright © 2015 Elsevier Inc. All rights reserved.

In Vitro Stretch Injury Induces Time- and Severity-Dependent Alterations of STEP Phosphorylation and Proteolysis in Neurons

PubMed Central

Mesfin, Mahlet N.; von Reyn, Catherine R.; Mott, Rosalind E.; Putt, Mary E.

2012-01-01

Abstract Striatal-enriched tyrosine phosphatase (STEP) has been identified as a component of physiological and pathophysiological signaling pathways mediated by N-methyl-d-aspartate (NMDA) receptor/calcineurin/calpain activation. Activation of these pathways produces a subsequent change in STEP isoform expression or activation via dephosphorylation. In this study, we evaluated changes in STEP phosphorylation and proteolysis in dissociated cortical neurons after sublethal and lethal mechanical injury using an in vitro stretch injury device. Sublethal stretch injury produces minimal changes in STEP phosphorylation at early time points, and increased STEP phosphorylation at 24 h that is blocked by the NMDA-receptor antagonist APV, the calcineurin-inhibitor FK506, and the sodium channel blocker tetrodotoxin. Lethal stretch injury produces rapid STEP dephosphorylation via NR2B-containing NMDA receptors, but not calcineurin, and a subsequent biphasic phosphorylation pattern. STEP61 expression progressively increases after sublethal stretch with no change in calpain-mediated STEP33 formation, while lethal stretch injury results in STEP33 formation via a NR2B-containing NMDA receptor pathway within 1 h of injury. Blocking calpain activation in the initial 30 min after stretch injury increases the ratio of active STEP in cells and blocks STEP33 formation, suggesting that STEP is an early substrate of calpain after mechanical injury. There is a strong correlation between the amount of STEP33 formed and the degree of cell death observed after lethal stretch injury. In summary, these data demonstrate that previously characterized pathways of STEP regulation via the NMDA receptor are generally conserved in mechanical injury, and suggest that calpain-mediated cleavage of STEP33 should be further examined as an early marker of neuronal fate after stretch injury. PMID:22435660

Unbalanced neuronal circuits in addiction.

PubMed

Volkow, Nora D; Wang, Gen-Jack; Tomasi, Dardo; Baler, Ruben D

2013-08-01

Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it. Published by Elsevier Ltd.

The Timing of Middle-Childhood Peer Rejection and Friendship: Linking Early Behavior to Early-Adolescent Adjustment

ERIC Educational Resources Information Center

Pedersen, Sara; Vitaro, Frank; Barker, Edward D.; Borge, Anne I. H.

2007-01-01

This study used a sample of 551 children surveyed yearly from ages 6 to 13 to examine the longitudinal associations among early behavior, middle-childhood peer rejection and friendedness, and early-adolescent depressive symptoms, loneliness, and delinquency. The study tested a sequential mediation hypothesis in which (a) behavior problems in the…

Comparing Indirect Effects in SEM: A Sequential Model Fitting Method Using Covariance-Equivalent Specifications

ERIC Educational Resources Information Center

Chan, Wai

2007-01-01

In social science research, an indirect effect occurs when the influence of an antecedent variable on the effect variable is mediated by an intervening variable. To compare indirect effects within a sample or across different samples, structural equation modeling (SEM) can be used if the computer program supports model fitting with nonlinear…

Attachment, Career-Choice Pessimism, and Intrinsic Motivation as Predictors of College Students' Career Adaptability

ERIC Educational Resources Information Center

Shin, Yun-Jeong; Lee, Ji-Yeon

2017-01-01

The purpose of this study was to examine the cross-cultural validity of the effects of attachment, career-choice pessimism, and intrinsic motivation on career adaptability (CA) in American (n = 198) and Korean (n = 294) college students. We hypothesized that the association between attachment and CA is sequentially mediated by career-choice…

Sequential Bimodal Bilingual Acquisition: Mediation Using a Cochlear Implant as a Tool

ERIC Educational Resources Information Center

Cramér-Wolrath, Emelie

2013-01-01

Most deaf children are born to hearing families. During the last twenty years deaf children, in increasing numbers and at an early age, receive a cochlear implant, a highly technological hearing device. The aim of this qualitative, longitudinal, single-case study was to explore and describe critical changes in naturalistic, video-observed…

Epimorphin acts extracellularly to promote cell sorting and aggregation during the condensation of vertebral cartilage.

PubMed

Oka, Yumiko; Sato, Yuki; Tsuda, Hokari; Hanaoka, Kazunori; Hirai, Yohei; Takahashi, Yoshiko

2006-03-01

Formation of vertebrae occurs via endochondral ossification, a process involving condensation of precartilaginous cells. Here, we provide the first molecular evidence of mechanism that underlies initiation of this process by showing that the extracellular factor, Epimorphin, plays a role during early steps in vertebral cartilage condensation. Epimorphin mRNA is predominantly localized in the vertebral primordium. When provided exogenously in ovo, it causes precocious differentiation of chondrocytes, resulting in the formation of supernumerary vertebral cartilage in chicken embryos. To further analyze its mode of action, we used an in vitro co-culture system in which labeled 10T1/2 or sclerotomal prechondrogenic cells were co-cultured with unlabeled Epimorphin-producing cells. In the presence of Epimorphin, the labeled cells formed tightly packed aggregates, and sclerotomal cells displayed augmented accumulation of NCAM and other early markers of chondrocyte differentiation. Finally, we found that the Epimorphin expression is initiated during vertebrogenesis by Sonic hedgehog from the notochord mediated by Sox 9. We present a model in which successive action of Epimorphin in recruiting and stacking sclerotomal cells leads to a sequential elongation of a vertebral primordium.

Dual-responsive immunosensor that combines colorimetric recognition and electrochemical response for ultrasensitive detection of cancer biomarkers.

PubMed

Hong, Wooyoung; Lee, Sooyeon; Cho, Youngnam

2016-12-15

We developed a nanoroughened, biotin-doped polypyrrole immunosensor for the detection of tumor markers through dual-signal (electrochemical and colorimetric) channels, electrochemical and colorimetric, that demonstrates remarkable analytical performance. A rapid, one-step electric field-mediated method was employed to fabricate the immunosensor with nanoscale roughness by simply modulating the applied electrical potential. We demonstrated the successful detection of three tumor markers (CA125, CEA, and PSA) via the double enzymatic signal amplifications in the presence of a target antigen, ultimately leading to desired diagnostic accuracy and reliability. The addition of multiple horseradish peroxidase (HRP)- and antibody-labeled nanoparticles greatly amplified the signal and simplified the measurement of cancer biomarker proteins by sequentially magnifying electrochemical and colorimetric signals in a single platform. The two parallel assays performed using the proposed immunosensor have yielded highly consistent and reproducible results. Additionally, for the analysis of plasma samples in a clinical setting, the values obtained with our immunosensor were validated by correlating the results with those of a standard radioimmunoassay (RIA), which obtained very similar clinically valid responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Surface structure characterization of Aspergillus fumigatus conidia mutated in the melanin synthesis pathway and their human cellular immune response.

PubMed

Bayry, Jagadeesh; Beaussart, Audrey; Dufrêne, Yves F; Sharma, Meenu; Bansal, Kushagra; Kniemeyer, Olaf; Aimanianda, Vishukumar; Brakhage, Axel A; Kaveri, Srini V; Kwon-Chung, Kyung J; Latgé, Jean-Paul; Beauvais, Anne

2014-08-01

In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Methods for integrating moderation and mediation: a general analytical framework using moderated path analysis.

PubMed

Edwards, Jeffrey R; Lambert, Lisa Schurer

2007-03-01

Studies that combine moderation and mediation are prevalent in basic and applied psychology research. Typically, these studies are framed in terms of moderated mediation or mediated moderation, both of which involve similar analytical approaches. Unfortunately, these approaches have important shortcomings that conceal the nature of the moderated and the mediated effects under investigation. This article presents a general analytical framework for combining moderation and mediation that integrates moderated regression analysis and path analysis. This framework clarifies how moderator variables influence the paths that constitute the direct, indirect, and total effects of mediated models. The authors empirically illustrate this framework and give step-by-step instructions for estimation and interpretation. They summarize the advantages of their framework over current approaches, explain how it subsumes moderated mediation and mediated moderation, and describe how it can accommodate additional moderator and mediator variables, curvilinear relationships, and structural equation models with latent variables. (c) 2007 APA, all rights reserved.

Manganese speciation of laboratory-generated welding fumes

PubMed Central

Andrews, Ronnee N.; Keane, Michael; Hanley, Kevin W.; Feng, H. Amy; Ashley, Kevin

2015-01-01

The objective of this laboratory study was to identify and measure manganese (Mn) fractions in chamber-generated welding fumes (WF) and to evaluate and compare the results from a sequential extraction procedure for Mn fractions with that of an acid digestion procedure for measurement of total, elemental Mn. To prepare Mn-containing particulate matter from representative welding processes, a welding system was operated in short circuit gas metal arc welding (GMAW) mode using both stainless steel (SS) and mild carbon steel (MCS) and also with flux cored arc welding (FCAW) and shielded metal arc welding (SMAW) using MCS. Generated WF samples were collected onto polycarbonate filters before homogenization, weighing and storage in scintillation vials. The extraction procedure consisted of four sequential steps to measure various Mn fractions based upon selective solubility: (1) soluble Mn dissolved in 0.01 M ammonium acetate; (2) Mn (0,II) dissolved in 25 % (v/v) acetic acid; (3) Mn (III,IV) dissolved in 0.5% (w/v) hydroxylamine hydrochloride in 25% (v/v) acetic acid; and (4) insoluble Mn extracted with concentrated hydrochloric and nitric acids. After sample treatment, the four fractions were analyzed for Mn by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). WF from GMAW and FCAW showed similar distributions of Mn species, with the largest concentrations of Mn detected in the Mn (0,II) and insoluble Mn fractions. On the other hand, the majority of the Mn content of SMAW fume was detected as Mn (III,IV). Although the concentration of Mn measured from summation of the four sequential steps was statistically significantly different from that measured from the hot block dissolution method for total Mn, the difference is small enough to be of no practical importance for industrial hygiene air samples, and either method may be used for Mn measurement. The sequential extraction method provides valuable information about the oxidation state of Mn in samples and allows for comparison to results from previous work and from total Mn dissolution methods. PMID:26345630

Effects of protonation on the hydrolysis of triphosphate in vacuum and the implications for catalysis by nucleotide hydrolyzing enzymes.

PubMed

Kiani, Farooq Ahmad; Fischer, Stefan

2016-06-29

Nucleoside triphosphate (NTP) hydrolysis is a key reaction in biology. It involves breaking two very stable bonds (one P-O bond and one O-H bond of water), in either a concurrent or a sequential way. Here, we systematically examine how protonation of the triphosphate affects the mechanism of hydrolysis. The hydrolysis reaction of methyl triphosphate in vacuum is computed with protons in various numbers and position on the three phosphate groups. Protonation is seen to have a strong catalytic effect, with the reaction mechanism depending highly on the protonation pattern. This dependence is apparently complicated, but is shown to obey a well-defined set of rules: Protonation of the α- and β-phosphate groups favors a sequential hydrolysis mechanism, whereas γ-protonation favors a concurrent mechanism, the two effects competing with each other in cases of simultaneous protonation. The rate-limiting step is always the breakup of the water molecule while it attacks the γ-phosphorus, and its barrier is lowered by γ-protonation. This step has significantly lower barriers in the sequential reactions, because the dissociated γ-metaphosphate intermediate (P γ O 3 - ) is a much better target for water attack than the un-dissociated γ-phosphate (-P γ O 4 2- ). The simple chemical logic behind these rules helps to better understand the catalytic strategy used by NTPase enzymes, as illustrated here for the catalytic pocket of myosin. A set of rules was determined that describes how protonating the phosphate groups affects the hydrolysis mechanism of methyl triphosphate: Protonation of the α- and/or β- phosphate groups promotes a sequential mechanism in which P-O bond breaking precedes the breakup of the attacking water, whereas protonation of the γ-phosphate promotes a concurrent mechanism and lowers the rate-limiting barrier of water breakup. The role played by individual protein residues in the catalytic pocket of triphosphate hydrolysing enzymes can be assigned accordingly.

Manganese speciation of laboratory-generated welding fumes.

PubMed

Andrews, Ronnee N; Keane, Michael; Hanley, Kevin W; Feng, H Amy; Ashley, Kevin

The objective of this laboratory study was to identify and measure manganese (Mn) fractions in chamber-generated welding fumes (WF) and to evaluate and compare the results from a sequential extraction procedure for Mn fractions with that of an acid digestion procedure for measurement of total, elemental Mn. To prepare Mn-containing particulate matter from representative welding processes, a welding system was operated in short circuit gas metal arc welding (GMAW) mode using both stainless steel (SS) and mild carbon steel (MCS) and also with flux cored arc welding (FCAW) and shielded metal arc welding (SMAW) using MCS. Generated WF samples were collected onto polycarbonate filters before homogenization, weighing and storage in scintillation vials. The extraction procedure consisted of four sequential steps to measure various Mn fractions based upon selective solubility: (1) soluble Mn dissolved in 0.01 M ammonium acetate; (2) Mn (0,II) dissolved in 25 % (v/v) acetic acid; (3) Mn (III,IV) dissolved in 0.5% (w/v) hydroxylamine hydrochloride in 25% (v/v) acetic acid; and (4) insoluble Mn extracted with concentrated hydrochloric and nitric acids. After sample treatment, the four fractions were analyzed for Mn by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). WF from GMAW and FCAW showed similar distributions of Mn species, with the largest concentrations of Mn detected in the Mn (0,II) and insoluble Mn fractions. On the other hand, the majority of the Mn content of SMAW fume was detected as Mn (III,IV). Although the concentration of Mn measured from summation of the four sequential steps was statistically significantly different from that measured from the hot block dissolution method for total Mn, the difference is small enough to be of no practical importance for industrial hygiene air samples, and either method may be used for Mn measurement. The sequential extraction method provides valuable information about the oxidation state of Mn in samples and allows for comparison to results from previous work and from total Mn dissolution methods.

Peer Support and Adolescents' Physical Activity: The Mediating Roles of Self-Efficacy and Enjoyment.

PubMed

Chen, Han; Sun, Haichun; Dai, Jun

2017-06-01

The present study aimed to contrast the mediating magnitude of self-efficacy and enjoyment connecting peer support and adolescents' physical activity (PA). Participants were 9th-12th grade students ( N  = 409; 56.5% boys) who were randomly chosen from six public schools located in Fuzhou city in southeast China. The bootstrapping method in structural equation modeling was conducted to examine the direct and indirect effects of peer support on adolescents' PA. Peer support did not directly impact PA. Rather, peer support indirectly influenced PA through either self-efficacy or enjoyment, with self-efficacy demonstrating a stronger mediating effect. Additionally, we found a significant serial mediating effect with enjoyment, and self-efficacy sequentially mediated the relationship between peer support and PA. The findings highlight the role of self-efficacy and enjoyment as mediators connecting peer support and PA. Self-efficacy seems to be more important, as it demonstrated a significantly greater mediating effect. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Sequential treatment for proctalgia fugax. Mid-term follow-up.

PubMed

Gracia Solanas, J A; Ramírez Rodríguez, J M; Elía Guedea, M; Aguilella Diago, V; Martínez Díez, M

2005-07-01

Proctalgia fugax (PF) is a benign, self-limiting disease characterized by episodes of intense anorectal pain at frequent intervals in the absence of organic proctological disease. Even though PF was described more than a century ago, its etiology remains unclear. Currently there is no information available. Few papers quoting many ways of management have been published. The aim of this study was to investigate patients complaining of this condition and to treat them with sequential therapy. We devised a descriptive, prospective study of patients complaining of acute perianal pain--duration less than 30 minutes--without organic disease or previous perianal surgery since 1996 to 2002 in our Department. We treated these patients using a three-step treatment (1: information, hip bath, benzodiazepines; 2: sublingual nifedipine 10 mg, or topic 0.1% nitroglycerin on demand; 3: internal anal sphincterotomy if hypertrophy of the internal anal sphincter was demonstrated by anal ultrasonography and no improvement was confirmed with the previous steps of treatment). We defined remarkable improvement as a decrease in the number of episodes by half or in pain intensity by 50%. Fifteen patients with an average follow-up of 4 years. Anal endosonography confirmed a grossly thickened internal anal sphincter (IAS) in 5 cases. After the first step of treatment 7 patients improved and 1 patient was cured; after the second step of treatment 3 patients improved and 1 was cured; the third step was applied to 3 patients with a thickened IAS; 1 patient improved and 1 patient was cured. A total resolution of PF is not always possible, but we may improve symptoms and their frequency. Almost 50% of patients in our series improved with the first step of treatment; 30% of our patients had IAS hypertrophy. Anal endosonography can help in the diagnosis of organic diseases or IAS hypertrophy, for which we can perform an internal anal sphincter myectomy.

Acceleration of linear stationary iterative processes in multiprocessor computers. II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romm, Ya.E.

1982-05-01

For pt.I, see Kibernetika, vol.18, no.1, p.47 (1982). For pt.I, see Cybernetics, vol.18, no.1, p.54 (1982). Considers a reduced system of linear algebraic equations x=ax+b, where a=(a/sub ij/) is a real n*n matrix; b is a real vector with common euclidean norm >>>. It is supposed that the existence and uniqueness of solution det (0-a) not equal to e is given, where e is a unit matrix. The linear iterative process converging to x x/sup (k+1)/=fx/sup (k)/, k=0, 1, 2, ..., where the operator f translates r/sup n/ into r/sup n/. In considering implementation of the iterative process (ip) inmore » a multiprocessor system, it is assumed that the number of processors is constant, and are various values of the latter investigated; it is assumed in addition, that the processors perform elementary binary arithmetic operations of addition and multiestimates only include the time of execution of arithmetic operations. With any paralleling of individual iteration, the execution time of the ip is proportional to the number of sequential steps k+1. The author sets the task of reducing the number of sequential steps in the ip so as to execute it in a time proportional to a value smaller than k+1. He also sets the goal of formulating a method of accelerated bit serial-parallel execution of each successive step of the ip, with, in the modification sought, a reduced number of steps in a time comparable to the operation time of logical elements. 6 references.« less

Attentional effects on orientation judgements are dependent on memory consolidation processes.

PubMed

Haskell, Christie; Anderson, Britt

2016-11-01

Are the effects of memory and attention on perception synergistic, antagonistic, or independent? Tested separately, memory and attention have been shown to affect the accuracy of orientation judgements. When multiple stimuli are presented sequentially versus simultaneously, error variance is reduced. When a target is validly cued, precision is increased. What if they are manipulated together? We combined memory and attention manipulations in an orientation judgement task to answer this question. Two circular gratings were presented sequentially or simultaneously. On some trials a brief luminance cue preceded the stimuli. Participants were cued to report the orientation of one of the two gratings by rotating a response grating. We replicated the finding that error variance is reduced on sequential trials. Critically, we found interacting effects of memory and attention. Valid cueing reduced the median, absolute error only when two stimuli appeared together and improved it to the level of performance on uncued sequential trials, whereas invalid cueing always increased error. This effect was not mediated by cue predictiveness; however, predictive cues reduced the standard deviation of the error distribution, whereas nonpredictive cues reduced "guessing". Our results suggest that, when the demand on memory is greater than a single stimulus, attention is a bottom-up process that prioritizes stimuli for consolidation. Thus attention and memory are synergistic.

Synchrotron x-ray study of a low roughness and high efficiency K 2 CsSb photocathode during film growth

DOE PAGES

Xie, Junqi; Demarteau, Marcel; Wagner, Robert; ...

2017-04-24

Reduction of roughness to the nm level is critical of achieving the ultimate performance from photocathodes used in high gradient fields. The thrust of this paper is to explore the evolution of roughness during sequential growth, and to show that deposition of multilayer structures consisting of very thin reacted layers results in an nm level smooth photocathode. Synchrotron x-ray methods were applied to study the multi-step growth process of a high efficiency K 2CsSb photocathode. We observed a transition point of the Sb film grown on Si at the film thickness of similar to 40 angstrom with the substrate temperaturemore » at 100 degrees C and the growth rate at 0.1 Å s -1. The final K 2CsSb photocathode exhibits a thickness of around five times that of the total deposited Sb film regardless of how the Sb film was grown. The film surface roughening process occurs first at the step when K diffuses into the crystalline Sb. Furthermore, the photocathode we obtained from the multi-step growth exhibits roughness in an order of magnitude lower than the normal sequential process. X-ray diffraction measurements show that the material goes through two structural changes of the crystalline phase during formation, from crystalline Sb to K 3Sb and finally to K 2CsSb.« less

Synchrotron x-ray study of a low roughness and high efficiency K 2 CsSb photocathode during film growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Junqi; Demarteau, Marcel; Wagner, Robert

Reduction of roughness to the nm level is critical of achieving the ultimate performance from photocathodes used in high gradient fields. The thrust of this paper is to explore the evolution of roughness during sequential growth, and to show that deposition of multilayer structures consisting of very thin reacted layers results in an nm level smooth photocathode. Synchrotron x-ray methods were applied to study the multi-step growth process of a high efficiency K 2CsSb photocathode. We observed a transition point of the Sb film grown on Si at the film thickness of similar to 40 angstrom with the substrate temperaturemore » at 100 degrees C and the growth rate at 0.1 Å s -1. The final K 2CsSb photocathode exhibits a thickness of around five times that of the total deposited Sb film regardless of how the Sb film was grown. The film surface roughening process occurs first at the step when K diffuses into the crystalline Sb. Furthermore, the photocathode we obtained from the multi-step growth exhibits roughness in an order of magnitude lower than the normal sequential process. X-ray diffraction measurements show that the material goes through two structural changes of the crystalline phase during formation, from crystalline Sb to K 3Sb and finally to K 2CsSb.« less

The association between daily steps and health, and the mediating role of body composition: a pedometer-based, cross-sectional study in an employed South African population.

PubMed

Pillay, Julian D; van der Ploeg, Hidde P; Kolbe-Alexander, Tracy L; Proper, Karin I; van Stralen, Maartje; Tomaz, Simone A; van Mechelen, Willem; Lambert, Estelle V

2015-02-22

Walking is recognized as an easily accessible mode of physical activity and is therefore supported as a strategy to promote health and well-being. To complement walking, pedometers have been identified as a useful tool for monitoring ambulatory physical activity, typically measuring total steps/day. There is, however, little information concerning dose-response for health outcomes in relation to intensity or duration of sustained steps. We aimed to examine this relationship, along with factors that mediate it, among employed adults. A convenience sample, recruited from work-site health risk screening (N = 312, 37 ± 9 yrs), wore a pedometer for at least three consecutive days. Steps were classified as "aerobic" (≥100 steps/minute and ≥10 consecutive minutes) or "non-aerobic" (<100 steps/minute and/or <10 consecutive minutes). The data were sub-grouped according to intensity-based categories i.e. "no aerobic activity", "low aerobic activity" (1-20 minutes/day of aerobic activity) and "high aerobic activity" (≥21 minutes/day of aerobic activity), with the latter used as a proxy for current PA guidelines (150-minutes of moderate-intensity PA per week). Health outcomes included blood pressure, body mass index, percentage body fat, waist circumference, blood cholesterol and blood glucose. Analysis of covariance, adjusting for age, gender and total steps/day were used to compare groups according to volume and intensity-based steps categories. A further analysis compared the mediation effect of body fat estimates (percentage body fat, body mass index and waist circumference) on the association between steps and health outcomes, independently. Average steps/day were 6,574 ± 3,541; total steps/day were inversely associated with most health outcomes in the expected direction (p < 0.05). The "no aerobic activity" group was significantly different from the "low aerobic activity" and "high aerobic activity" in percentage body fat and diastolic blood pressure only (P < 0.05). Percentage body fat emerged as the strongest mediator of the relationship between steps and outcomes, while body mass index showed the least mediation effect. The study provides a presentation of cross-sectional pedometer data that relate to a combination of intensity and volume-based steps/day and its relationship to current guidelines. The integration of volume, intensity and duration of ambulatory physical activity in pedometer-based messages is of emerging relevance.

Enhanced planar perovskite solar cell efficiency and stability using a perovskite/PCBM heterojunction formed in one step.

PubMed

Zhou, Long; Chang, Jingjing; Liu, Ziye; Sun, Xu; Lin, Zhenhua; Chen, Dazheng; Zhang, Chunfu; Zhang, Jincheng; Hao, Yue

2018-02-08

Perovskite/PCBM heterojunctions are efficient for fabricating perovskite solar cells with high performance and long-term stability. In this study, an efficient perovskite/PCBM heterojunction was formed via conventional sequential deposition and one-step formation processes. Compared with conventional deposition, the one-step process was more facile, and produced a perovskite thin film of substantially improved quality due to fullerene passivation. Moreover, the resulting perovskite/PCBM heterojunction exhibited more efficient carrier transfer and extraction, and reduced carrier recombination. The perovskite solar cell device based on one-step perovskite/PCBM heterojunction formation exhibited a higher maximum PCE of 17.8% compared with that from the conventional method (13.7%). The device also showed exceptional stability, retaining 83% of initial PCE after 60 days of storage under ambient conditions.

Collagenase-3 binds to a specific receptor and requires the low density lipoprotein receptor-related protein for internalization

NASA Technical Reports Server (NTRS)

Barmina, O. Y.; Walling, H. W.; Fiacco, G. J.; Freije, J. M.; Lopez-Otin, C.; Jeffrey, J. J.; Partridge, N. C.

1999-01-01

We have previously identified a specific receptor for collagenase-3 that mediates the binding, internalization, and degradation of this ligand in UMR 106-01 rat osteoblastic osteosarcoma cells. In the present study, we show that collagenase-3 binding is calcium-dependent and occurs in a variety of cell types, including osteoblastic and fibroblastic cells. We also present evidence supporting a two-step mechanism of collagenase-3 binding and internalization involving both a specific collagenase-3 receptor and the low density lipoprotein receptor-related protein. Ligand blot analysis shows that (125)I-collagenase-3 binds specifically to two proteins ( approximately 170 kDa and approximately 600 kDa) present in UMR 106-01 cells. Western blotting identified the 600-kDa protein as the low density lipoprotein receptor-related protein. Our data suggest that the 170-kDa protein is a specific collagenase-3 receptor. Low density lipoprotein receptor-related protein-null mouse embryo fibroblasts bind but fail to internalize collagenase-3, whereas UMR 106-01 and wild-type mouse embryo fibroblasts bind and internalize collagenase-3. Internalization, but not binding, is inhibited by the 39-kDa receptor-associated protein. We conclude that the internalization of collagenase-3 requires the participation of the low density lipoprotein receptor-related protein and propose a model in which the cell surface interaction of this ligand requires a sequential contribution from two receptors, with the collagenase-3 receptor acting as a high affinity primary binding site and the low density lipoprotein receptor-related protein mediating internalization.

Sequential protein unfolding through a carbon nanotube pore

NASA Astrophysics Data System (ADS)

Xu, Zhonghe; Zhang, Shuang; Weber, Jeffrey K.; Luan, Binquan; Zhou, Ruhong; Li, Jingyuan

2016-06-01

An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable ``unfoldon'' motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability.An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable ``unfoldon'' motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00410e

Thematic Unit Planning in Social Studies: Make It Focused and Meaningful

ERIC Educational Resources Information Center

Horton, Todd A.; Barnett, Jennifer A.

2008-01-01

Unit planning is perhaps the most difficult of the teacher duties to execute well. This paper offers suggestions for improving focus and increasing the meaningfulness of thematic unit content for students. Stressing the concept of a Big Understanding, it outlines 6 sequential steps in the creation of units which, when applied, not only establish a…

A Serious Look at the 4MAT Model.

ERIC Educational Resources Information Center

Scott, Harry V.

4MAT is an 8-step, sequential instructional model based on two theoretical constructs: Kolb's model of learning styles and the concept of brain hemisphericity. The model, developed by B. McCarthy (1987), is derived by interacting each of Kolb's four quadrants with both left and right brain. Kolb outlined four learning styles based on the four…

Context Dependence of One-Question-per-Passage Measures of Reading Comprehension.

ERIC Educational Resources Information Center

Oaster, T. R. F.; And Others

This study hypothesized that items in the one-question-per-passage format would be less easily answered when administered without their associated contexts than conventional reading comprehension items. A total of 256 seventh and eighth grade students were administered both Forms 3A and 3B of the Sequential Tests of Educational Progress (STEP 11).…

Japan’s Growing Technological Capability: Implications for the U.S. Economy

DTIC Science & Technology

1992-01-01

lineup of people who understood the problem and were eager to solve it. They included the following: Lionel Olmer, Clyde Pre- stowitz, and William... sequential process steps (of per- haps two dozen or so different but repeated types) to produce the finished device. It might well be thought that in this zase

The Influence of Student Characteristics on Early Elementary Oral Reading Fluency

ERIC Educational Resources Information Center

van Dijk, Wilhelmina

2018-01-01

Oral Reading Fluency (ORF) is a widely-used index of reading ability in early elementary grades; however, little information exists on predictive value of student characteristics on ORF scores (Wang, Algozzine, Ma, & Porfeli, 2011). A three-step sequential model was used to analyze the influence of student characteristics on scores (N = 2649)…

Translation of Evidence-Based Practices in a Behaviour Support Implementation Model for Youth with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Lyons, Gregory

2011-01-01

Linda Miller describes a model for the practical implementation of behaviour supports. This model, the "5P approach", attempts to delineate a comprehensive and sequentially-stepped model of the assessment and treatment of challenging behaviour with consistent colour-coded themes. The 5Ps include profiling the child, prioritising the challenging…

Divergent pathways to influence: Cognition and behavior differentially mediate the effects of optimism on physical and mental quality of life in Chinese university students.

PubMed

Ramsay, Jonathan E; Yang, Fang; Pang, Joyce S; Lai, Ching-Man; Ho, Roger Cm; Mak, Kwok-Kei

2015-07-01

Previous research has indicated that both cognitive and behavioral variables mediate the positive effect of optimism on quality of life; yet few attempts have been made to accommodate these constructs into a single explanatory framework. Adopting Fredrickson's broaden-and-build perspective, we examined the relationships between optimism, self-rated health, resilience, exercise, and quality of life in 365 Chinese university students using path analysis. For physical quality of life, a two-stage model, in which the effects of optimism were sequentially mediated by cognitive and behavioral variables, provided the best fit. A one-stage model, with full mediation by cognitive variables, provided the best fit for mental quality of life. This suggests that optimism influences physical and mental quality of life via different pathways. © The Author(s) 2013.

Sequential disinfection of E. coli O157:H7 on shredded lettuce leaves by aqueous chlorine dioxide, ozonated water, and thyme essential oil

NASA Astrophysics Data System (ADS)

Singh, Nepal; Singh, Rakesh K.; Bhunia, Arun K.; Stroshine, Richard L.; Simon, James E.

2001-03-01

There have been numerous studies on effectiveness of different sanitizers for microbial inactivation. However, results obtained from different studies indicate that microorganism cannot be easily removed from fresh cut vegetables because of puncture and cut surfaces with varying surface topographies. In this study, three step disinfection approach was evaluated for inactivation of E. coli O157:H7 on shredded lettuce leaves. Sequential application of thyme oil, ozonated water, and aqueous chlorine dioxide was evaluated in which thyme oil was applied first followed by ozonated water and aqueous chlorine dioxide. Shredded lettuce leaves inoculated with cocktail culture of E. coli O157:H7 (C7927, EDL 933 and 204 P), were washed with ozonated water (15 mg/l for 10min), aqueous chlorine dioxide (10 mg/l,for 10min) and thyme oil suspension (0.1%, v/v for 5min). Washing of lettuce leaves with ozonated water, chlorine dioxide and thyme oil suspension resulted in 0.44, 1.20, and 1.46 log reduction (log10 cfu/g), respectively. However, the sequential treatment achieved approximately 3.13 log reductions (log10 cfu/g). These results demonstrate the efficacy of sequential treatments in decontaminating shredded lettuce leaves containing E. coli O157:H7.

Method for sequentially processing a multi-level interconnect circuit in a vacuum chamber

NASA Technical Reports Server (NTRS)

Routh, D. E.; Sharma, G. C. (Inventor)

1984-01-01

An apparatus is disclosed which includes a vacuum system having a vacuum chamber in which wafers are processed on rotating turntables. The vacuum chamber is provided with an RF sputtering system and a dc magnetron sputtering system. A gas inlet introduces various gases to the vacuum chamber and creates various gas plasma during the sputtering steps. The rotating turntables insure that the respective wafers are present under the sputtering guns for an average amount of time such that consistency in sputtering and deposition is achieved. By continuous and sequential processing of the wafers in a common vacuum chamber without removal, the adverse affects of exposure to atmospheric conditions are eliminated providing higher quality circuit contacts and functional device.

Article and method of forming an article

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lacy, Benjamin Paul; Kottilingam, Srikanth Chandrudu; Dutta, Sandip

Provided are an article and a method of forming an article. The method includes providing a metallic powder, heating the metallic powder to a temperature sufficient to joint at least a portion of the metallic powder to form an initial layer, sequentially forming additional layers in a build direction by providing a distributed layer of the metallic powder over the initial layer and heating the distributed layer of the metallic powder, repeating the steps of sequentially forming the additional layers in the build direction to form a portion of the article having a hollow space formed in the build direction,more » and forming an overhang feature extending into the hollow space. The article includes an article formed by the method described herein.« less

Sequentially Executed Model Evaluation Framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

2015-10-20

Provides a message passing framework between generic input, model and output drivers, and specifies an API for developing such drivers. Also provides batch and real-time controllers which step the model and I/O through the time domain (or other discrete domain), and sample I/O drivers. This is a library framework, and does not, itself, solve any problems or execute any modeling. The SeMe framework aids in development of models which operate on sequential information, such as time-series, where evaluation is based on prior results combined with new data for this iteration. Has applications in quality monitoring, and was developed as partmore » of the CANARY-EDS software, where real-time water quality data is being analyzed for anomalies.« less

Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair.

PubMed

Min, Jouha; Choi, Ki Young; Dreaden, Erik C; Padera, Robert F; Braatz, Richard D; Spector, Myron; Hammond, Paula T

2016-04-26

Infections associated with orthopedic implants cause increased morbidity and significant healthcare cost. A prolonged and expensive two-stage procedure requiring two surgical steps and a 6-8 week period of joint immobilization exists as today's gold standard for the revision arthroplasty of an infected prosthesis. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a continually growing part of the population. Here, we demonstrate that a single-stage revision using prostheses coated with self-assembled, hydrolytically degradable multilayers that sequentially deliver the antibiotic (gentamicin) and the osteoinductive growth factor (BMP-2) in a time-staggered manner enables both eradication of established biofilms and complete and rapid bone tissue repair around the implant in rats with induced osteomyelitis. The nanolayered construct allows precise independent control of release kinetics and loading for each therapeutic agent in an infected implant environment. Antibiotics contained in top layers can be tuned to provide a rapid release at early times sufficient to eliminate infection, followed by sustained release for several weeks, and the underlying BMP-2 component enables a long-term sustained release of BMP-2, which induced more significant and mechanically competent bone formation than a short-term burst release. The successful growth factor-mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength 15-fold when compared with the uncoated one. These findings demonstrate the potential of this layered release strategy to introduce a durable next-generation implant solution, ultimately an important step forward to future large animal models toward the clinic.

In vitro analysis of human immunodeficiency virus particle dissociation: gag proteolytic processing influences dissociation kinetics.

PubMed

Müller, Barbara; Anders, Maria; Reinstein, Jochen

2014-01-01

Human immunodeficiency virus particles undergo a step of proteolytic maturation, in which the main structural polyprotein Gag is cleaved into its mature subunits matrix (MA), capsid (CA), nucleocapsid (NC) and p6. Gag proteolytic processing is accompanied by a dramatic structural rearrangement within the virion, which is necessary for virus infectivity and has been proposed to proceed through a sequence of dissociation and reformation of the capsid lattice. Morphological maturation appears to be tightly regulated, with sequential cleavage events and two small spacer peptides within Gag playing important roles by regulating the disassembly of the immature capsid layer and formation of the mature capsid lattice. In order to measure the influence of individual Gag domains on lattice stability, we established Förster's resonance energy transfer (FRET) reporter virions and employed rapid kinetic FRET and light scatter measurements. This approach allowed us to measure dissociation properties of HIV-1 particles assembled in eukaryotic cells containing Gag proteins in different states of proteolytic processing. While the complex dissociation behavior of the particles prevented an assignment of kinetic rate constants to individual dissociation steps, our analyses revealed characteristic differences in the dissociation properties of the MA layer dependent on the presence of additional domains. The most striking effect observed here was a pronounced stabilization of the MA-CA layer mediated by the presence of the 14 amino acid long spacer peptide SP1 at the CA C-terminus, underlining the crucial role of this peptide for the resolution of the immature particle architecture.

Longitudinal Linkages among Parent-Child Acculturation Discrepancy, Parenting, Parent-Child Sense of Alienation, and Adolescent Adjustment in Chinese Immigrant Families

ERIC Educational Resources Information Center

Kim, Su Yeong; Chen, Qi; Wang, Yijie; Shen, Yishan; Orozco-Lapray, Diana

2013-01-01

Parent-child acculturation discrepancy is a risk factor in the development of children in immigrant families. Using a longitudinal sample of Chinese immigrant families, the authors of the current study examined how unsupportive parenting and parent-child sense of alienation sequentially mediate the relationship between parent-child acculturation…

Regioselective Cu(I)-catalyzed tandem A3-coupling/decarboxylative coupling to 3-amino-1,4-enynes.

PubMed

Feng, Huangdi; Ermolat'ev, Denis S; Song, Gonghua; Van der Eycken, Erik V

2012-04-06

An efficient and novel copper-mediated protocol for the synthesis of 3-amino-1,4-enynes from glyoxylic acid, an amine, and an alkyne was developed. This new reaction involving two sequential C-C bond formations is air and moisture tolerant and proceeds via a tandem A(3)-coupling and a selective decarboxylative coupling.

Synthesis of cyclic, multivalent Arg-Gly-Asp using sequential thiol-ene/thiol-yne photoreactions

PubMed Central

Aimetti, Alex A.; Feaver, Kristen R.

2014-01-01

A unique method has been developed for the formation of multivalent cyclic peptides. This procedure exploits on-resin peptide cyclization using a photoinitiated thiol-ene click reaction and subsequent clustering using thiol-yne photochemistry. Both reactions utilize the sulfhydryl group on natural cysteine amino acids to participate in the thiol-mediated reactions. PMID:20552127

Self-Inference and the Foot-in-the-Door Technique: Quantity of Behavior and Attitudinal Mediation.

ERIC Educational Resources Information Center

Dillard, James Price

1990-01-01

Investigates the self-perception theory account of the foot-in-the-door (FITD) phenomenon, a sequential-request technique using a small first request followed by a larger, target request. Finds that a self-inference explanation is viable, but that a strict self-perception account fails because neither request size nor execution correspond to…

Advanced treatment of residual nitrogen from biologically treated coke effluent by a microalga-mediated process using volatile fatty acids (VFAs) under stepwise mixotrophic conditions.

PubMed

Ryu, Byung-Gon; Kim, Woong; Heo, Sung-Woon; Kim, Donghyun; Choi, Gang-Guk; Yang, Ji-Won

2015-09-01

This work describes the development of a microalga-mediated process for simultaneous removal of residual ammonium nitrogen (NH4(+)-N) and production of lipids from biologically treated coke effluent. Four species of green algae were tested using a sequential mixotrophic process. In the first phase-CO2-supplied mixotrophic condition-all microalgae assimilated NH4(+)-N with no evident inhibition. In second phase-volatile fatty acids (VFAs)-supplied mixotrophic condition-removal rates of NH4(+)-N and biomass significantly increased. Among the microalgae used, Arctic Chlorella sp. ArM0029B had the highest rate of NH4(+)-N removal (0.97 mg/L/h) and fatty acid production (24.9 mg/L/d) which were 3.6- and 2.1-fold higher than those observed under the CO2-supplied mixotrophic condition. Redundancy analysis (RDA) indicated that acetate and butyrate were decisive factors for increasing NH4(+)-N removal and fatty acid production. These results demonstrate that microalgae can be used in a sequential process for treatment of residual nitrogen after initial treatment of activated sludge. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unusual behavior in magnesium-copper cluster matter produced by helium droplet mediated deposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emery, S. B., E-mail: samuel.emery@navy.mil; Little, B. K.; Air Force Research Laboratory, Munitions Directorate, 2306 Perimeter Rd., Eglin AFB, Florida 32542

2015-02-28

We demonstrate the ability to produce core-shell nanoclusters of materials that typically undergo intermetallic reactions using helium droplet mediated deposition. Composite structures of magnesium and copper were produced by sequential condensation of metal vapors inside the 0.4 K helium droplet baths and then gently deposited onto a substrate for analysis. Upon deposition, the individual clusters, with diameters ∼5 nm, form a cluster material which was subsequently characterized using scanning and transmission electron microscopies. Results of this analysis reveal the following about the deposited cluster material: it is in the un-alloyed chemical state, it maintains a stable core-shell 5 nm structuremore » at sub-monolayer quantities, and it aggregates into unreacted structures of ∼75 nm during further deposition. Surprisingly, high angle annular dark field scanning transmission electron microscopy images revealed that the copper appears to displace the magnesium at the core of the composite cluster despite magnesium being the initially condensed species within the droplet. This phenomenon was studied further using preliminary density functional theory which revealed that copper atoms, when added sequentially to magnesium clusters, penetrate into the magnesium cores.« less

Stepwise sequential redox potential modulation possible on a single platform.

PubMed

Pepiol, Ariadna; Teixidor, Francesc; Sillanpää, Reijo; Lupu, Marius; Viñas, Clara

2011-12-23

Step by step: The cluster [3,3'-Co(1,2-C(2)B(9)H(11))(2)](-) is an excellent platform for making a stepwise tunable redox potential system by dehydroiodination. With the addition of up to eight iodine substituents (purple; see picture), there is a fall in the E(1/2)(Co(III)/Co(II)) value from -1.80 V to -0.68 V (vs. Fc(+)/Fc; Fc = ferrocene). A practical application of this tunability has been observed in the growth of polypyrrole. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Brief Report: Clustered Forward Chaining with Embedded Mastery Probes to Teach Recipe Following.

PubMed

Chazin, Kate T; Bartelmay, Danielle N; Lambert, Joseph M; Houchins-Juárez, Nealetta J

2017-04-01

This study evaluated the effectiveness of a clustered forward chaining (CFC) procedure to teach a 23-year-old male with autism to follow written recipes. CFC incorporates elements of forward chaining (FC) and total task chaining (TTC) by teaching a small number of steps (i.e., units) using TTC, introducing new units sequentially (akin to FC), and prompting through untrained steps. Results indicated that CFC was effective for teaching the participant to follow written recipes. Results maintained with therapist support for 3-5 weeks for all recipes, and maintained when therapist support was removed.

A C–H oxidation approach for streamlining synthesis of chiral polyoxygenated motifs

PubMed Central

Covell, Dustin J.; White, M. Christina

2013-01-01

Chiral oxygenated molecules are pervasive in natural products and medicinal agents; however, their chemical syntheses often necessitate numerous, wasteful steps involving functional group and oxidation state manipulations. Herein a strategy for synthesizing a readily diversifiable class of chiral building blocks, allylic alcohols, through sequential asymmetric C—H activation/resolution is evaluated against the state-of-the-art. The C—H oxidation routes’ capacity to strategically introduce oxygen into a sequence and thereby minimize non-productive manipulations is demonstrated to effect significant decreases in overall step-count and increases in yield and synthetic flexibility. PMID:25013239

Statistical process control: a practical application for hospitals.

PubMed

VanderVeen, L M

1992-01-01

A six-step plan based on using statistics was designed to improve quality in the central processing and distribution department of a 223-bed hospital in Oakland, CA. This article describes how the plan was implemented sequentially, starting with the crucial first step of obtaining administrative support. The QI project succeeded in overcoming beginners' fear of statistics and in training both managers and staff to use inspection checklists, Pareto charts, cause-and-effect diagrams, and control charts. The best outcome of the program was the increased commitment to quality improvement by the members of the department.

A 2-step penalized regression method for family-based next-generation sequencing association studies.

PubMed

Ding, Xiuhua; Su, Shaoyong; Nandakumar, Kannabiran; Wang, Xiaoling; Fardo, David W

2014-01-01

Large-scale genetic studies are often composed of related participants, and utilizing familial relationships can be cumbersome and computationally challenging. We present an approach to efficiently handle sequencing data from complex pedigrees that incorporates information from rare variants as well as common variants. Our method employs a 2-step procedure that sequentially regresses out correlation from familial relatedness and then uses the resulting phenotypic residuals in a penalized regression framework to test for associations with variants within genetic units. The operating characteristics of this approach are detailed using simulation data based on a large, multigenerational cohort.

Sequential improvements in organ procurement increase the organ donation rate.

PubMed

Billeter, Adrian T; Sklare, Seth; Franklin, Glen A; Wright, Jerry; Morgan, Gary; O'Flynn, Paul E; Polk, Hiram C

2012-11-01

Organ demand exceeds availability of transplantable organs. Organ procurement continues to suffer from failures to identify potential donors, inability to obtain consent for donation, as well as failures to retrieve certain organs as donor demographics change. The purpose of this article is to propose how sequentially introduced measures can increase organ donation rates as well as improve organ procurement. We analysed the effect of stepwise improvements in the organ procurement process patients in a university-based surgical intensive care unit over a 20-year period. We related newly introduced measures in the organ retrieval process with changes in donation rates. We specifically targeted these three main steps in the donation process: donor identification, conversion of potential donors to actual donors, and organ protection during the procurement process. Finally, we assessed the effect of the same measures on organ procurement after introduction in other hospitals of the same organ procurement region. Introduction of quality improvement steps increased all of the observed parameters. The number of organ donors was stabilised due to a better identification of potential donors, a major increase in conversion from potential to actual donors, and an increase in extended criteria donor. Improvements in organ protection led to higher rates of organs transplanted per donor and increased recovery of lungs and hearts despite increasing donor age. The same measures were introduced successfully in other hospitals in our organ procurement region. Sequential improvements in organ procurement can increase the yield of retrieved organs. The same measures can be applied to other hospitals and lead to comparable improvements in organ donation. Published by Elsevier Ltd.

Semimembranosus Release for Medial Soft Tissue Balancing Does Not Weaken Knee Flexion Strength in Patients Undergoing Varus Total Knee Arthroplasty.

PubMed

Jang, Sung Won; Koh, In Jun; Kim, Man Soo; Kim, Ju Yeong; In, Yong

2016-11-01

The sequential medial release technique including semimembranosus (semiM) release is effective and safe during varus total knee arthroplasty (TKA). However, there are concerns about weakening of knee flexion strength after semiM release. We determined whether semiM release to balance the medial soft tissue decreased knee flexion strength after TKA. Fifty-nine consecutive varus knees undergoing TKA were prospectively enrolled. A 3-step sequential release protocol which consisted of release of (1) the deep medial collateral ligament (dMCL), (2) the semiM, and (3) the superficial medial collateral ligament based on medial tightness. Gap balancing was obtained after dMCL release in 31 knees. However, 28 knees required semiM release or more after dMCL release. Isometric muscle strength of the knee was compared 6 months postoperatively between the semiM release and semiM nonrelease groups. Knee stability and clinical outcomes were also compared. No differences in knee flexor or extensor peak torque were observed between the groups 6 months postoperatively (P = .322 and P = .383, respectively). No group difference was observed in medial joint opening angle on valgus stress radiographs (P = .327). No differences in the Knee Society or Western Ontario and McMaster Universities Osteoarthritis Index scores were detected between the groups (P = .840 and P = .682, respectively). These results demonstrate that semiM release as a sequential step to balance medial soft tissue in varus knees did not affect knee flexion strength after TKA. Copyright © 2016 Elsevier Inc. All rights reserved.

Sequential enzymatic derivatization coupled with online microdialysis sampling for simultaneous profiling of mouse tumor extracellular hydrogen peroxide, lactate, and glucose.

PubMed

Su, Cheng-Kuan; Tseng, Po-Jen; Chiu, Hsien-Ting; Del Vall, Andrea; Huang, Yu-Fen; Sun, Yuh-Chang

2017-03-01

Probing tumor extracellular metabolites is a vitally important issue in current cancer biology. In this study an analytical system was constructed for the in vivo monitoring of mouse tumor extracellular hydrogen peroxide (H 2 O 2 ), lactate, and glucose by means of microdialysis (MD) sampling and fluorescence determination in conjunction with a smart sequential enzymatic derivatization scheme-involving a loading sequence of fluorogenic reagent/horseradish peroxidase, microdialysate, lactate oxidase, pyruvate, and glucose oxidase-for step-by-step determination of sampled H 2 O 2 , lactate, and glucose in mouse tumor microdialysate. After optimization of the overall experimental parameters, the system's detection limit reached as low as 0.002 mM for H 2 O 2 , 0.058 mM for lactate, and 0.055 mM for glucose, based on 3 μL of microdialysate, suggesting great potential for determining tumor extracellular concentrations of lactate and glucose. Spike analyses of offline-collected mouse tumor microdialysate and monitoring of the basal concentrations of mouse tumor extracellular H 2 O 2 , lactate, and glucose, as well as those after imparting metabolic disturbance through intra-tumor administration of a glucose solution through a prior-implanted cannula, were conducted to demonstrate the system's applicability. Our results evidently indicate that hyphenation of an MD sampling device with an optimized sequential enzymatic derivatization scheme and a fluorescence spectrometer can be used successfully for multi-analyte monitoring of tumor extracellular metabolites in living animals. Copyright © 2016 Elsevier B.V. All rights reserved.

Fractionation of metals by sequential extraction procedures (BCR and Tessier) in soil exposed to fire of wide temperature range

NASA Astrophysics Data System (ADS)

Fajkovic, Hana; Rončević, Sanda; Nemet, Ivan; Prohić, Esad; Leontić-Vazdar, Dana

2017-04-01

Forest fire presents serious problem, especially in Mediterranean Region. Effects of fire are numerous, from climate change and deforestation to loss of soil organic matter and changes in soil properties. One of the effects, not well documented, is possible redistribution and/or remobilisation of pollutants previously deposited in the soil, due to the new physical and chemical soil properties and changes in equilibrium conditions. For understanding and predicting possible redistribution and/or remobilisation of potential pollutants from soil, affected by fire different in temperature, several laboratory investigations were carried out. To evaluate the influence of organic matter on soil under fire, three soil samples were analysed and compared: (a) the one with added coniferous organic matter; (b) deciduous organic matter (b) and (c) soil without additional organic matter. Type of organic matter is closely related to pH of soil, as pH is influencing the mobility of some pollutants, e.g. metals. For that reason pH was also measured through all experimental steps. Each of mentioned soil samples (a, b and c) were heated at 1+3 different temperatures (25°C, 200°C, 500°C and 850°C). After heating, whereby fire effect on soil was simulated, samples were analysed by BCR protocol with the addition of a first step of sequential extraction procedure by Tessier and analysis of residual by aqua regia. Element fractionation of heavy metals by this procedure was used to determine the amounts of selected elements (Al, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb and Zn). Selected metal concentrations were determined using inductively coupled plasma atomic emission spectrometer. Further on, loss of organic matter was calculated after each heating procedure as well as the mineral composition. The mineral composition was determined using an X-ray diffraction. From obtained results, it can be concluded that temperature has an influence on concentration of elements in specific step of sequential extraction procedures. The first step of Tessier and BCR extraction of samples heated at 250°C and 500°C showed increasing trend of elemental concentrations. Results of these steps are especially important since they indicate mobile fraction of the elements (exchangeable, water- and acid-soluble fraction), which can easily affect the environment. Extraction procedures of samples combusted at 850°C showed that decrease in measured elemental content occurred. Some correlation is also noticed between type of organic matter, pH and concentration of analysed elements.

The Temporal Sequence of Social Anxiety and Depressive Symptoms following Interpersonal Stressors during Adolescence

PubMed Central

Hamilton, Jessica L.; Potter, Carrie M.; Olino, Thomas M.; Abramson, Lyn Y.; Heimberg, Richard G.; Alloy, Lauren B.

2015-01-01

Social anxiety and depressive symptoms dramatically increase and frequently co-occur during adolescence. Although research indicates that general interpersonal stressors, peer victimization, and familial emotional maltreatment predict symptoms of social anxiety and depression, it remains unclear how these stressors contribute to the sequential development of these internalizing symptoms. Thus, the present study examined the sequential development of social anxiety and depressive symptoms following the occurrence of interpersonal stressors, peer victimization, and familial emotional maltreatment. Participants included 410 early adolescents (53% female; 51% African American; Mean age =12.84 years) who completed measures of social anxiety and depressive symptoms at three time points (Times 1–3), as well as measures of general interpersonal stressors, peer victimization, and emotional maltreatment at Time 2. Path analyses revealed that interpersonal stressors, peer victimization, and emotional maltreatment predicted both depressive and social anxiety symptoms concurrently. However, depressive symptoms significantly mediated the pathway from interpersonal stressors, peer victimization, and familial emotional maltreatment to subsequent levels of social anxiety symptoms. In contrast, social anxiety did not mediate the relationship between these stressors and subsequent depressive symptoms. There was no evidence of sex or racial differences in these mediational pathways. Findings suggest that interpersonal stressors, including the particularly detrimental stressors of peer victimization and familial emotional maltreatment, may predict both depressive and social anxiety symptoms; however, adolescents who have more immediate depressogenic reactions may be at greater risk for later development of symptoms of social anxiety. PMID:26142495

The relationship between counselors' technical skills, clients' in-session verbal responses, and outcome in smoking cessation treatment.

PubMed

Lindqvist, Helena; Forsberg, Lars; Enebrink, Pia; Andersson, Gerhard; Rosendahl, Ingvar

2017-06-01

The technical component of Motivational Interviewing (MI) posits that client language mediates the relationship between counselor techniques and subsequent client behavioral outcomes. The purpose of this study was to examine this hypothesized technical component of MI in smoking cessation treatment in more depth. Secondary analysis of 106 first treatment sessions, derived from the Swedish National Tobacco Quitline, and previously rated using the Motivational Interviewing Sequential Code for Observing Process Exchanges (MI-SCOPE) Coder's Manual and the Motivational Interviewing Treatment Integrity code (MITI) Manual, version 3.1. The outcome measure was self-reported 6-month continuous abstinence at 12-month follow-up. Sequential analyses indicated that clients were significantly more likely than expected by chance to argue for change (change talk) following MI-consistent behaviors and questions and reflections favoring change. Conversely, clients were more likely to argue against change (sustain talk) following questions and reflections favoring status-quo. Parallel mediation analysis revealed that a counselor technique (reflections of client sustain talk) had an indirect effect on smoking outcome at follow-up through client language mediators. The study makes a significant contribution to our understanding of how MI works in smoking cessation treatment and adds further empirical support for the hypothesized technical component in MI. The results emphasize the importance of counselors avoiding unintentional reinforcement of sustain talk and underline the need for a greater emphasis on the direction of questions and reflections in MI trainings and fidelity measures. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of action control and action planning on fruit and vegetable consumption.

PubMed

Zhou, Guangyu; Gan, Yiqun; Miao, Miao; Hamilton, Kyra; Knoll, Nina; Schwarzer, Ralf

2015-08-01

Globally, fruit and vegetable intake is lower than recommended despite being an important component to a healthy diet. Adopting or maintaining a sufficient amount of fruit and vegetables in one's diet may require not only motivation but also self-regulatory processes. Action control and action planning are two key volitional determinants that have been identified in the literature; however, it is not fully understood how these two factors operate between intention and behavior. Thus, the aim of the current study was to explore the roles of action control and action planning as mediators between intentions and dietary behavior. A longitudinal study with three points in time was conducted. Participants (N = 286) were undergraduate students and invited to participate in a health behavior survey. At baseline (Time 1), measures of intention and fruit and vegetable intake were assessed. Two weeks later (Time 2), action control and action planning were assessed as putative sequential mediators. At Time 3 (two weeks after Time 2), fruit and vegetable consumption was measured as the outcome. The results revealed action control and action planning to sequentially mediate between intention and subsequent fruit and vegetable intake, controlling for baseline behavior. Both self-regulatory constructs, action control and action planning, make a difference when moving from motivation to action. Our preliminary evidence, therefore, suggests that planning may be more proximal to fruit and vegetable intake than action control. Further research, however, needs to be undertaken to substantiate this conclusion. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Temporal Sequence of Social Anxiety and Depressive Symptoms Following Interpersonal Stressors During Adolescence.

PubMed

Hamilton, Jessica L; Potter, Carrie M; Olino, Thomas M; Abramson, Lyn Y; Heimberg, Richard G; Alloy, Lauren B

2016-04-01

Social anxiety and depressive symptoms dramatically increase and frequently co-occur during adolescence. Although research indicates that general interpersonal stressors, peer victimization, and familial emotional maltreatment predict symptoms of social anxiety and depression, it remains unclear how these stressors contribute to the sequential development of these internalizing symptoms. Thus, the present study examined the sequential development of social anxiety and depressive symptoms following the occurrence of interpersonal stressors, peer victimization, and familial emotional maltreatment. Participants included 410 early adolescents (53% female; 51% African American; Mean age =12.84 years) who completed measures of social anxiety and depressive symptoms at three time points (Times 1-3), as well as measures of general interpersonal stressors, peer victimization, and emotional maltreatment at Time 2. Path analyses revealed that interpersonal stressors, peer victimization, and emotional maltreatment predicted both depressive and social anxiety symptoms concurrently. However, depressive symptoms significantly mediated the pathway from interpersonal stressors, peer victimization, and familial emotional maltreatment to subsequent levels of social anxiety symptoms. In contrast, social anxiety did not mediate the relationship between these stressors and subsequent depressive symptoms. There was no evidence of sex or racial differences in these mediational pathways. Findings suggest that interpersonal stressors, including the particularly detrimental stressors of peer victimization and familial emotional maltreatment, may predict both depressive and social anxiety symptoms; however, adolescents who have more immediate depressogenic reactions may be at greater risk for later development of symptoms of social anxiety.

Coach autonomy support and quality of sport engagement in young soccer players.

PubMed

Alvarez, María Sol; Balaguer, Isabel; Castillo, Isabel; Duda, Joan L

2009-05-01

Based on the self-determination theory (Ryan & Deci, 2000), this study tested a model of the assumed sequential relationships between perceived autonomy support, psychological need satisfaction, self-determined motivation, and enjoyment/boredom. The hypothesized mediational roles of psychological need satisfaction and self-determined motivation were also studied. In a sample of 370 young male soccer players, path analysis results offered support for the proposed model. Total mediation was supported in the case of the psychological need satisfaction in the relationship between autonomy support and self-determined motivation, and partial mediation for self-determined motivation in the links between psychological need satisfaction and enjoyment (positive) and boredom (negative). Implications of autonomy-supportive behaviors provided by coaches for the quality of sport involvement among young athletes are discussed.

Do material, psychosocial and behavioural factors mediate the relationship between disability acquisition and mental health? A sequential causal mediation analysis.

PubMed

Aitken, Zoe; Simpson, Julie Anne; Gurrin, Lyle; Bentley, Rebecca; Kavanagh, Anne Marie

2018-01-29

There is evidence of a causal relationship between disability acquisition and poor mental health; however, the mechanism by which disability affects mental health is poorly understood. This gap in understanding limits the development of effective interventions to improve the mental health of people with disabilities. We used four waves of data from the Household, Income and Labour Dynamics in Australia Survey (2011-14) to compare self-reported mental health between individuals who acquired any disability (n=387) and those who remained disability-free (n=7936). We tested three possible pathways from disability acquisition to mental health, examining the effect of material, psychosocial and behavioural mediators. The effect was partitioned into natural direct and indirect effects through the mediators using a sequential causal mediation analysis approach. Multiple imputation using chained equations was used to assess the impact of missing data. Disability acquisition was estimated to cause a five-point decline in mental health [estimated mean difference: -5.3, 95% confidence interval (CI) -6.8, -3.7]. The indirect effect through material factors was estimated to be a 1.7-point difference (-1.7, 95% CI -2.8, -0.6), explaining 32% of the total effect, with a negligible proportion of the effect explained by the addition of psychosocial characteristics (material and psychosocial: -1.7, 95% CI -3.0, -0.5) and a further 5% by behavioural factors (material-psychosocial-behavioural: -2.0, 95% CI -3.4, -0.6). The finding that the effect of disability acquisition on mental health operates predominantly through material rather than psychosocial and behavioural factors has important implications. The results highlight the need for better social protection, including income support, employment and education opportunities, and affordable housing for people who acquire a disability. © The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

When the Test of Mediation is More Powerful than the Test of the Total Effect

PubMed Central

O'Rourke, Holly P.; MacKinnon, David P.

2014-01-01

Although previous research has studied power in mediation models, the extent to which the inclusion of a mediator will increase power has not been investigated. First, a study compared analytical power of the mediated effect to the total effect in a single mediator model to identify the situations in which the inclusion of one mediator increased statistical power. Results from the first study indicated that including a mediator increased statistical power in small samples with large coefficients and in large samples with small coefficients, and when coefficients were non-zero and equal across models. Next, a study identified conditions where power was greater for the test of the total mediated effect compared to the test of the total effect in the parallel two mediator model. Results indicated that including two mediators increased power in small samples with large coefficients and in large samples with small coefficients, the same pattern of results found in the first study. Finally, a study assessed analytical power for a sequential (three-path) two mediator model and compared power to detect the three-path mediated effect to power to detect both the test of the total effect and the test of the mediated effect for the single mediator model. Results indicated that the three-path mediated effect had more power than the mediated effect from the single mediator model and the test of the total effect. Practical implications of these results for researchers are then discussed. PMID:24903690

Novel Regulation of Skp1 by the Dictyostelium AgtA α-Galactosyltransferase Involves the Skp1-binding Activity of Its WD40 Repeat Domain*

PubMed Central

Schafer, Christopher M.; Sheikh, M. Osman; Zhang, Dongmei; West, Christopher M.

2014-01-01

The role of Skp1 as an adaptor protein that links Cullin-1 to F-box proteins in E3 Skp1/Cullin-1/F-box protein (SCF) ubiquitin ligases is well characterized. In the social amoeba Dictyostelium and probably many other unicellular eukaryotes, Skp1 is modified by a pentasaccharide attached to a hydroxyproline near its C terminus. This modification is important for oxygen-sensing during Dictyostelium development and is mediated by a HIF-α type prolyl 4-hydroxylase and five sequentially acting cytoplasmic glycosyltransferase activities. Gene disruption studies show that AgtA, the enzyme responsible for addition of the final two galactose residues, in α-linkages to the Skp1 core trisaccharide, is unexpectedly critical for oxygen-dependent terminal development. AgtA possesses a WD40 repeat domain C-terminal to its single catalytic domain and, by use of domain deletions, binding studies, and enzyme assays, we find that the WD40 repeats confer a salt-sensitive second-site binding interaction with Skp1 that mediates novel catalytic activation in addition to simple substrate recognition. In addition, AgtA binds similarly well to precursor isoforms of Skp1 by a salt-sensitive mechanism that competes with binding to an F-box protein and recognition by early modification enzymes, and the effect of binding is diminished when AgtA modifies Skp1. Genetic studies show that loss of AgtA is more severe when an earlier glycosylation step is blocked, and overexpressed AgtA is deleterious if catalytically inactivated. Together, the findings suggest that AgtA mediates non-enzymatic control of unmodified and substrate precursor forms of Skp1 by a binding mechanism that is normally relieved by switch-like activation of its glycosylation function. PMID:24550398

Anticipating conflict facilitates controlled stimulus-response selection

PubMed Central

Correa, Ángel; Rao, Anling; Nobre, Anna C.

2014-01-01

Cognitive control can be triggered in reaction to previous conflict, as suggested by the finding of sequential effects in conflict tasks. Can control also be triggered proactively by presenting cues predicting conflict (‘proactive control’)? We exploited the high temporal resolution of event-related potentials (ERPs) and controlled for sequential effects to ask whether proactive control based on anticipating conflict modulates neural activity related to cognitive control, as may be predicted from the conflict-monitoring model. ERPs associated with conflict detection (N2) were measured during a cued flanker task. Symbolic cues were either informative or neutral with respect to whether the target involved conflicting or congruent responses. Sequential effects were controlled by analysing the congruency of the previous trial. The results showed that cuing conflict facilitated conflict resolution and reduced the N2 latency. Other potentials (frontal N1 and P3) were also modulated by cuing conflict. Cuing effects were most evident after congruent than after incongruent trials. This interaction between cuing and sequential effects suggests neural overlap between the control networks triggered by proactive and reactive signals. This finding clarifies why previous neuroimaging studies, in which reactive sequential effects were not controlled, have rarely found anticipatory effects upon conflict-related activity. Finally, the high temporal resolution of ERPs was critical to reveal a temporal modulation of conflict detection by proactive control. This novel finding suggests that anticipating conflict speeds up conflict detection and resolution. Recent research suggests that this anticipatory mechanism may be mediated by pre-activation of the ACC during the preparatory interval. PMID:18823248

CRISPR/Cas9-mediated gene targeting in Arabidopsis using sequential transformation.

PubMed

Miki, Daisuke; Zhang, Wenxin; Zeng, Wenjie; Feng, Zhengyan; Zhu, Jian-Kang

2018-05-17

Homologous recombination-based gene targeting is a powerful tool for precise genome modification and has been widely used in organisms ranging from yeast to higher organisms such as Drosophila and mouse. However, gene targeting in higher plants, including the most widely used model plant Arabidopsis thaliana, remains challenging. Here we report a sequential transformation method for gene targeting in Arabidopsis. We find that parental lines expressing the bacterial endonuclease Cas9 from the egg cell- and early embryo-specific DD45 gene promoter can improve the frequency of single-guide RNA-targeted gene knock-ins and sequence replacements via homologous recombination at several endogenous sites in the Arabidopsis genome. These heritable gene targeting can be identified by regular PCR. Our approach enables routine and fine manipulation of the Arabidopsis genome.

The Twelve Promises of Alcoholics Anonymous: psychometric measure validation and mediational testing as a 12-step specific mechanism of behavior change.

PubMed

Kelly, John F; Greene, M Claire

2013-12-01

Empirical support for the recovery utility of 12-step mutual-help organizations (MHOs) has led to increased investigation of how such organizations confer benefit. The Twelve Promises of Alcoholics Anonymous (AA) feature prominently in 12-step philosophy and culture and are one of the few documented explications of the cognitive, affective, and behavioral benefits that members might accrue. This study investigated the psychometric properties of a measure of AA's Twelve Promises and examined whether it mediated the effect of 12-step participation on abstinence. Young adults (N=302, M age 20.4 [1.6], range 18-25; 27% female; 95% White) enrolled in an addiction treatment effectiveness study completed assessments at intake and 3-, 6-, and 12-months post treatment including a 26-item, Twelve Promises Scale (TPS). Factor analyses examined the TPS' psychometrics and lagged mediational analyses tested the TPS as a mechanism of behavior change. Robust principal axis factoring extraction with Varimax rotation revealed a 2-factor solution explaining 45-58% of the variance across three administrations ("Psychological Wellbeing"=26-39%; "Freedom from Craving=17-21%); internal consistency was high (alpha=.83-.93). Both factors were found to increase in relation to greater 12-step participation, but significant mediation was found only for the Freedom from Craving factor explaining 21-34% of the effect of 12-step participation in increasing abstinence. The TPS shows potential as a conceptually relevant, and psychometrically sound measure and may be useful in helping elucidate the extent to which the Twelve Promises emerge as an independent benefit of 12-step participation and/or explain SUD remission and recovery. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Analysis of Dibenzothiophene Desulfurization in a Recombinant Pseudomonas putida Strain▿

PubMed Central

Calzada, Javier; Zamarro, María T.; Alcón, Almudena; Santos, Victoria E.; Díaz, Eduardo; García, José L.; Garcia-Ochoa, Felix

2009-01-01

Biodesulfurization was monitored in a recombinant Pseudomonas putida CECT5279 strain. DszB desulfinase activity reached a sharp maximum at the early exponential phase, but it rapidly decreased at later growth phases. A model two-step resting-cell process combining sequentially P. putida cells from the late and early exponential growth phases was designed to significantly increase biodesulfurization. PMID:19047400

Brief Report: Clustered Forward Chaining with Embedded Mastery Probes to Teach Recipe Following

ERIC Educational Resources Information Center

Chazin, Kate T.; Bartelmay, Danielle N.; Lambert, Joseph M.; Houchins-Juárez, Nealetta J.

2017-01-01

This study evaluated the effectiveness of a clustered forward chaining (CFC) procedure to teach a 23-year-old male with autism to follow written recipes. CFC incorporates elements of forward chaining (FC) and total task chaining (TTC) by teaching a small number of steps (i.e., units) using TTC, introducing new units sequentially (akin to FC), and…

Forest management planning for timber production: a sequential approach

Treesearch

Krishna P. Rustagi

1978-01-01

Explicit forest management planning for timber production beyond the first few years at any time necessitates use of information which can best be described as suspect. The two-step approach outlined here concentrates on the planning strategy over the next few years without losing sight of the long-run productivity. Frequent updating of the long-range and short-range...

The Goal Wheel: Adapting Navajo Philosophy and the Medicine Wheel to Work with Adolescents

ERIC Educational Resources Information Center

Garner, Holly; Bruce, Mary Alice; Stellern, John

2011-01-01

The purpose of this article is to describe a group counseling model that is based on the indigenous medicine wheel as well as Navajo philosophy by which to help troubled adolescents restore harmony and balance in their lives, through establishing goals and sequential steps to accomplish these goals. The authors call this model the Goal Wheel. A…

THE LIBERATION OF ARSENOSUGARS FROM MATRIX COMPONENTS IN DIFFICULT TO EXTRACT SEAFOOD SAMPLES UTILIZING TMAOH/ACETIC ACID SEQUENTIALLY IN A TWO-STAGE EXTRACTION PROCESS

EPA Science Inventory

Sample extraction is one of the most important steps in arsenic speciation analysis of solid dietary samples. One of the problem areas in this analysis is the partial extraction of arsenicals from seafood samples. The partial extraction allows the toxicity of the extracted arse...

How to Ask for a Favor: An Exploration of Speech Act Pragmatics in Heritage Russian

ERIC Educational Resources Information Center

Dubinina, Irina Yevgenievna

2012-01-01

Heritage language (HL) is a linguistic system that arises in the context of early childhood bilingualism, both sequential and simultaneous, when one of the languages is not fully acquired. The performance of speech acts in HLs is yet to be understood, and this dissertation is a first step in this direction. The study investigates the pragmatic…

Neuromuscular disease classification system

NASA Astrophysics Data System (ADS)

Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M.; Serrano, Carmen

2013-06-01

Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns.

Cooperative mechanism of RNA packaging motor.

PubMed

Lísal, Jirí; Tuma, Roman

2005-06-17

P4 is a hexameric ATPase that serves as the RNA packaging motor in double-stranded RNA bacteriophages from the Cystoviridae family. P4 shares sequence and structural similarities with hexameric helicases. A structure-based mechanism for mechano-chemical coupling has recently been proposed for P4 from bacteriophage phi12. However, coordination of ATP hydrolysis among the subunits and coupling with RNA translocation remains elusive. Here we present detailed kinetic study of nucleotide binding, hydrolysis, and product release by phi12 P4 in the presence of different RNA and DNA substrates. Whereas binding affinities for ATP and ADP are not affected by RNA binding, the hydrolysis step is accelerated and the apparent cooperativity is increased. No nucleotide binding cooperativity is observed. We propose a stochastic-sequential cooperativity model to describe the coordination of ATP hydrolysis within the hexamer. In this model the apparent cooperativity is a result of hydrolysis stimulation by ATP and RNA binding to neighboring subunits rather than cooperative nucleotide binding. The translocation step appears coupled to hydrolysis, which is coordinated among three neighboring subunits. Simultaneous interaction of neighboring subunits with RNA makes the otherwise random hydrolysis sequential and processive.

Growth and Characterization of Pyrite Thin Films for Photovoltaic Applications

NASA Astrophysics Data System (ADS)

Wertheim, Alex

A series of pyrite thin films were synthesized using a novel sequential evaporation technique to study the effects of substrate temperature on deposition rate and micro-structure of the deposited material. Pyrite was deposited in a monolayer-by-monolayer fashion using sequential evaporation of Fe under high vacuum, followed by sulfidation at high S pressures (typically > 1 mTorr to 1 Torr). Thin films were synthesized using two different growth processes; a one-step process in which a constant growth temperature is maintained throughout growth, and a three-step process in which an initial low temperature seed layer is deposited, followed by a high temperature layer, and then finished with a low temperature capping layer. Analysis methods to analyze the properties of the films included Glancing Angle X-Ray Diffraction (GAXRD), Rutherford Back-scattering Spectroscopy (RBS), Transmission Electron Microscopy (TEM), Secondary Ion Mass Spectroscopy (SIMS), 2-point IV measurements, and Hall effect measurements. Our results show that crystallinity of the pyrite thin film improves and grain size increases with increasing substrate temperature. The sticking coefficient of Fe was found to increase with increasing growth temperature, indicating that the Fe incorporation into the growing film is a thermally activated process.

Laboratory Formation of Fullerenes from PAHs: Top-down Interstellar Chemistry

NASA Astrophysics Data System (ADS)

Zhen, Junfeng; Castellanos, Pablo; Paardekooper, Daniel M.; Linnartz, Harold; Tielens, Alexander G. G. M.

2014-12-01

Interstellar molecules are thought to build up in the shielded environment of molecular clouds or in the envelope of evolved stars. This follows many sequential reaction steps of atoms and simple molecules in the gas phase and/or on (icy) grain surfaces. However, these chemical routes are highly inefficient for larger species in the tenuous environment of space as many steps are involved and, indeed, models fail to explain the observed high abundances. This is definitely the case for the C60 fullerene, recently identified as one of the most complex molecules in the interstellar medium. Observations have shown that, in some photodissociation regions, its abundance increases close to strong UV-sources. In this Letter we report laboratory findings in which C60 formation can be explained by characterizing the photochemical evolution of large polycyclic aromatic hydrocarbons (PAHs). Sequential H losses lead to fully dehydrogenated PAHs and subsequent losses of C2 units convert graphene into cages. Our results present for the first time experimental evidence that PAHs in excess of 60 C-atoms efficiently photo-isomerize to buckminsterfullerene, C60. These laboratory studies also attest to the importance of top-down synthesis routes for chemical complexity in space.

One-pot Sequential Reactions Featuring a Copper-catalyzed Amination Leading to Pyrido[2',1':2,3]imidazo[4,5-c]quinolines and Dihydropyrido[2',1':2,3]imidazo[4,5-c]quinolines.

PubMed

Fan, Xue-Sen; Zhang, Ju; Li, Bin; Zhang, Xin-Ying

2015-06-01

Tetracyclic skeletons combining an imidazo[1,2-a]pyridine moiety with a quinoline framework such as pyrido[2',1':2,3]imidazo[4,5-b]quinoline are stimulating increasing interests since they are close isosteres of a series of powerful antiproliferative compounds. In this paper, we report a novel methodology for the synthesis of pyrido[2',1':2,3]imidazo[4,5-c]quinolines through one-pot sequential reactions of commercially available or readily obtainable 2-aminopyridines, 2-bromophenacyl bromides, aqueous ammonia, and aldehydes. Moreover, dihydropyrido[2',1':2,3]imidazo[4,5-c]quinolines could also be obtained in a similar manner by using various ketones as the substrates in place of aldehydes. Notably, the whole procedure combines condensation/amination/cyclization reactions in one pot to give complex compounds in a simple and practical manner. Compared with literature methods, the synthetic strategy reported herein has the advantages of readily available starting materials, structural diversity of products, good functional group tolerance, and obviation of step-by-step operations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ensemble Sampling vs. Time Sampling in Molecular Dynamics Simulations of Thermal Conductivity

DOE PAGES

Gordiz, Kiarash; Singh, David J.; Henry, Asegun

2015-01-29

In this report we compare time sampling and ensemble averaging as two different methods available for phase space sampling. For the comparison, we calculate thermal conductivities of solid argon and silicon structures, using equilibrium molecular dynamics. We introduce two different schemes for the ensemble averaging approach, and show that both can reduce the total simulation time as compared to time averaging. It is also found that velocity rescaling is an efficient mechanism for phase space exploration. Although our methodology is tested using classical molecular dynamics, the ensemble generation approaches may find their greatest utility in computationally expensive simulations such asmore » first principles molecular dynamics. For such simulations, where each time step is costly, time sampling can require long simulation times because each time step must be evaluated sequentially and therefore phase space averaging is achieved through sequential operations. On the other hand, with ensemble averaging, phase space sampling can be achieved through parallel operations, since each ensemble is independent. For this reason, particularly when using massively parallel architectures, ensemble sampling can result in much shorter simulation times and exhibits similar overall computational effort.« less

Dance-the-Music: an educational platform for the modeling, recognition and audiovisual monitoring of dance steps using spatiotemporal motion templates

NASA Astrophysics Data System (ADS)

Maes, Pieter-Jan; Amelynck, Denis; Leman, Marc

2012-12-01

In this article, a computational platform is presented, entitled "Dance-the-Music", that can be used in a dance educational context to explore and learn the basics of dance steps. By introducing a method based on spatiotemporal motion templates, the platform facilitates to train basic step models from sequentially repeated dance figures performed by a dance teacher. Movements are captured with an optical motion capture system. The teachers' models can be visualized from a first-person perspective to instruct students how to perform the specific dance steps in the correct manner. Moreover, recognition algorithms-based on a template matching method-can determine the quality of a student's performance in real time by means of multimodal monitoring techniques. The results of an evaluation study suggest that the Dance-the-Music is effective in helping dance students to master the basics of dance figures.

Unmasking the masked Universe: the 2M++ catalogue through Bayesian eyes

NASA Astrophysics Data System (ADS)

Lavaux, Guilhem; Jasche, Jens

2016-01-01

This work describes a full Bayesian analysis of the Nearby Universe as traced by galaxies of the 2M++ survey. The analysis is run in two sequential steps. The first step self-consistently derives the luminosity-dependent galaxy biases, the power spectrum of matter fluctuations and matter density fields within a Gaussian statistic approximation. The second step makes a detailed analysis of the three-dimensional large-scale structures, assuming a fixed bias model and a fixed cosmology. This second step allows for the reconstruction of both the final density field and the initial conditions at z = 1000 assuming a fixed bias model. From these, we derive fields that self-consistently extrapolate the observed large-scale structures. We give two examples of these extrapolation and their utility for the detection of structures: the visibility of the Sloan Great Wall, and the detection and characterization of the Local Void using DIVA, a Lagrangian based technique to classify structures.

Residue behaviour of six pesticides in button crimini during home canning.

PubMed

Du, Pengqiang; Liu, Xingang; Gu, Xiaojun; Dong, Fengshou; Xu, Jun; Kong, Zhiqiang; Li, Yuanbo; Zheng, Yongquan

2014-01-01

The effect of home canning (including washing, boiling, cooling, adding solution and sterilisation) on residue levels of imidacloprid, diflubenzuron, abamectin, pyriproxyfen and β-cypermethrin and chlorothalonilin on button crimini was assessed. Residues of imidacloprid, diflubenzuron, abamectin and pyriproxyfen were measured by UPLC-MS/MS; the residues of β-cypermethrin and chlorothalonil were measured by GC. Results showed that washing resulted in a 3.8% reduction of the initial residue level of imidacloprid (p ≤ 0.05). From washing to sterilisation the processing effect was significant compared with raw crimini (p ≤ 0.05), but processing through cooling and adding solution had no effect. For diflubenzuron, from raw crimini to sterilisation the processing effect was significant by comparison with the initial level (p ≤ 0.05); the processing effect was not obvious between two sequential steps, and the sequential steps have list: washing and boiling, boiling and cooling, boiling and adding of solution, cooling and adding solution. The changes in abamectin levels were also significant from raw crimini to sterilisation compared with raw crimini (p ≤ 0.05), but the changes were not obvious from boiling to adding solution and amongst them. For pyriproxyfen, washing resulted in a 39% reduction, but changes were not obvious from washing to sterilisation, p ≤ 0.05 between two consecutive steps. The whole procedure could significantly decrease residues of β-cypermethrin (p ≤ 0.05); washing could significantly reduce residues of β-cypermethrin; the effects of last procedures were complicated, and p ≤ 0.05 between two consecutive steps. Washing resulted in an 80% reduction of chlorothalonil; after washing there were no detectable residues. After the whole process, the processing factors for imidacloprid, diflubenzuron, abamectin, pyriproxyfen, β-cypermethrin and chlorothalonil were 0.40, 0.22, 0.04, 0.85, 0.28 and 0, respectively.

Single step biotransformation of corn oil phytosterols to boldenone by a newly isolated Pseudomonas aeruginosa.

PubMed

Eisa, Mohamed; El-Refai, Heba; Amin, Magdy

2016-09-01

A new potent Pseudomonas aeruginosa isolate capable for biotransformation of corn oil phytosterol (PS) to 4-androstene-3, 17-dione (AD), testosterone (T) and boldenone (BOL) was identified by phenotypic analysis and 16S rRNA gene sequencing. Sequential statistical strategy was used to optimize the biotransformation process mainly concerning BOL using Factorial design and response surface methodology (RSM). The production of BOL in single step microbial biotransformation from corn oil phytosterols by P. aeruginosa was not previously reported. Results showed that the pH concentration of the medium, (NH 4 ) 2 SO 4 and KH 2 PO 4 were the most significant factors affecting BOL production. By analyzing the statistical model of three-dimensional surface plot, BOL production increased from 36.8% to 42.4% after the first step of optimization, and the overall biotransformation increased to 51.9%. After applying the second step of the sequential statistical strategy BOL production increased to 53.6%, and the overall biotransformation increased to 91.9% using the following optimized medium composition (g/l distilled water) (NH 4 ) 2 SO 4 , 2; KH 2 PO 4 , 4; Na 2 HPO 4 . 1; MgSO 4 ·7H 2 O, 0.3; NaCl, 0.1; CaCl 2 ·2H 2 O, 0.1; FeSO 4 ·7H 2 O, 0.001; ammonium acetate 0.001; Tween 80, 0.05%; corn oil 0.5%; 8-hydroxyquinoline 0.016; pH 8; 200 rpm agitation speed and incubation time 36 h at 30 °C. Validation experiments proved the adequacy and accuracy of model, and the results showed the predicted value agreed well with the experimental values.

Biomass pyrolysis liquid to citric acid via 2-step bioconversion.

PubMed

Yang, Zhiguang; Bai, Zhihui; Sun, Hongyan; Yu, Zhisheng; Li, Xingxing; Guo, Yifei; Zhang, Hongxun

2014-12-31

The use of fossil carbon sources for fuels and petrochemicals has serious impacts on our environment and is unable to meet the demand in the future. A promising and sustainable alternative is to substitute fossil carbon sources with microbial cell factories converting lignocellulosic biomass into desirable value added products. However, such bioprocesses require tolerance to inhibitory compounds generated during pretreatment of biomass. In this study, the process of sequential two-step bio-conversion of biomass pyrolysis liquid containing levoglucosan (LG) to citric acid without chemical detoxification has been explored, which can greatly improve the utilization efficiency of lignocellulosic biomass. The sequential two-step bio-conversion of corn stover pyrolysis liquid to citric acid has been established. The first step conversion by Phanerochaete chrysosporium (P. chrysosporium) is desirable to decrease the content of other compounds except levoglucosan as a pretreatment for the second conversion. The remaining levoglucosan in solution was further converted into citric acid by Aspergillus niger (A. niger) CBX-209. Thus the conversion of cellulose to citric acid is completed by both pyrolysis and bio-conversion technology. Under experimental conditions, levoglucosan yield is 12% based on the feedstock and the citric acid yield can reach 82.1% based on the levoglucosan content in the pyrolysis liquid (namely 82.1 g of citric acid per 100 g of levoglucosan). The study shows that P. chrysosporium and A. niger have the potential to be used as production platforms for value-added products from pyrolyzed lignocellulosic biomass. Selected P. chrysosporium is able to decrease the content of other compounds except levoglucosan and levoglucosan can be further converted into citric acid in the residual liquids by A. niger. Thus the conversion of cellulose to citric acid is completed by both pyrolysis and bio-conversion technology.

Semi-automated hydrophobic interaction chromatography column scouting used in the two-step purification of recombinant green fluorescent protein.

PubMed

Stone, Orrin J; Biette, Kelly M; Murphy, Patrick J M

2014-01-01

Hydrophobic interaction chromatography (HIC) most commonly requires experimental determination (i.e., scouting) in order to select an optimal chromatographic medium for purifying a given target protein. Neither a two-step purification of untagged green fluorescent protein (GFP) from crude bacterial lysate using sequential HIC and size exclusion chromatography (SEC), nor HIC column scouting elution profiles of GFP, have been previously reported. Bacterial lysate expressing recombinant GFP was sequentially adsorbed to commercially available HIC columns containing butyl, octyl, and phenyl-based HIC ligands coupled to matrices of varying bead size. The lysate was fractionated using a linear ammonium phosphate salt gradient at constant pH. Collected HIC eluate fractions containing retained GFP were then pooled and further purified using high-resolution preparative SEC. Significant differences in presumptive GFP elution profiles were observed using in-line absorption spectrophotometry (A395) and post-run fluorimetry. SDS-PAGE and western blot demonstrated that fluorometric detection was the more accurate indicator of GFP elution in both HIC and SEC purification steps. Comparison of composite HIC column scouting data indicated that a phenyl ligand coupled to a 34 µm matrix produced the highest degree of target protein capture and separation. Conducting two-step protein purification using the preferred HIC medium followed by SEC resulted in a final, concentrated product with >98% protein purity. In-line absorbance spectrophotometry was not as precise of an indicator of GFP elution as post-run fluorimetry. These findings demonstrate the importance of utilizing a combination of detection methods when evaluating purification strategies. GFP is a well-characterized model protein, used heavily in educational settings and by researchers with limited protein purification experience, and the data and strategies presented here may aid in development other of HIC-compatible protein purification schemes.

On-Site Production of Cellulolytic Enzymes by the Sequential Cultivation Method.

PubMed

Farinas, Cristiane S; Florencio, Camila; Badino, Alberto C

2018-01-01

The conversion of renewable lignocellulosic biomass into fuels, chemicals, and high-value materials using the biochemical platform has been considered the most sustainable alternative for the implementation of future biorefineries. However, the high cost of the cellulolytic enzymatic cocktails used in the saccharification step significantly affects the economics of industrial large-scale conversion processes. The on-site production of enzymes, integrated to the biorefinery plant, is being considered as a potential strategy that could be used to reduce costs. In such approach, the microbial production of enzymes can be carried out using the same lignocellulosic biomass as feedstock for fungal development and biofuels production. Most of the microbial cultivation processes for the production of industrial enzymes have been developed using the conventional submerged fermentation. Recently, a sequential solid-state followed by submerged fermentation has been described as a potential alternative cultivation method for cellulolytic enzymes production. This chapter presents the detailed procedure of the sequential cultivation method, which could be employed for the on-site production of the cellulolytic enzymes required to convert lignocellulosic biomass into simple sugars.

Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin

PubMed Central

Ziani, Salim; Nagy, Zita; Alekseev, Sergey; Soutoglou, Evi; Egly, Jean-Marc

2014-01-01

In nucleotide excision repair (NER), damage recognition by XPC-hHR23b is described as a critical step in the formation of the preincision complex (PInC) further composed of TFIIH, XPA, RPA, XPG, and ERCC1-XPF. To obtain new molecular insights into the assembly of the PInC, we analyzed its formation independently of DNA damage by using the lactose operator/repressor reporter system. We observed a sequential and ordered self-assembly of the PInC operating upon immobilization of individual NER factors on undamaged chromatin and mimicking that functioning on a bona fide NER substrate. We also revealed that the recruitment of the TFIIH subunit TTDA, involved in trichothiodystrophy group A disorder (TTD-A), was key in the completion of the PInC. TTDA recruits XPA through its first 15 amino acids, depleted in some TTD-A patients. More generally, these results show that proteins forming large nuclear complexes can be recruited sequentially on chromatin in the absence of their natural DNA target and with no reciprocity in their recruitment. PMID:25154395

Testing Quantum Models of Conjunction Fallacy on the World Wide Web

NASA Astrophysics Data System (ADS)

Aerts, Diederik; Arguëlles, Jonito Aerts; Beltran, Lester; Beltran, Lyneth; de Bianchi, Massimiliano Sassoli; Sozzo, Sandro; Veloz, Tomas

2017-12-01

The `conjunction fallacy' has been extensively debated by scholars in cognitive science and, in recent times, the discussion has been enriched by the proposal of modeling the fallacy using the quantum formalism. Two major quantum approaches have been put forward: the first assumes that respondents use a two-step sequential reasoning and that the fallacy results from the presence of `question order effects'; the second assumes that respondents evaluate the cognitive situation as a whole and that the fallacy results from the `emergence of new meanings', as an `effect of overextension' in the conceptual conjunction. Thus, the question arises as to determine whether and to what extent conjunction fallacies would result from `order effects' or, instead, from `emergence effects'. To help clarify this situation, we propose to use the World Wide Web as an `information space' that can be interrogated both in a sequential and non-sequential way, to test these two quantum approaches. We find that `emergence effects', and not `order effects', should be considered the main cognitive mechanism producing the observed conjunction fallacies.

In-situ sequential laser transfer and laser reduction of graphene oxide films

NASA Astrophysics Data System (ADS)

Papazoglou, S.; Petridis, C.; Kymakis, E.; Kennou, S.; Raptis, Y. S.; Chatzandroulis, S.; Zergioti, I.

2018-04-01

Achieving high quality transfer of graphene on selected substrates is a priority in device fabrication, especially where drop-on-demand applications are involved. In this work, we report an in-situ, fast, simple, and one step process that resulted in the reduction, transfer, and fabrication of reduced graphene oxide-based humidity sensors, using picosecond laser pulses. By tuning the laser illumination parameters, we managed to implement the sequential printing and reduction of graphene oxide flakes. The overall process lasted only a few seconds compared to a few hours that our group has previously published. DC current measurements, X-Ray Photoelectron Spectroscopy, X-Ray Diffraction, and Raman Spectroscopy were employed in order to assess the efficiency of our approach. To demonstrate the applicability and the potential of the technique, laser printed reduced graphene oxide humidity sensors with a limit of detection of 1700 ppm are presented. The results demonstrated in this work provide a selective, rapid, and low-cost approach for sequential transfer and photochemical reduction of graphene oxide micro-patterns onto various substrates for flexible electronics and sensor applications.

Sequential and simultaneous strategies for biorefining of wheat straw using room temperature ionic liquids, xylanases and cellulases.

PubMed

Husson, Eric; Auxenfans, Thomas; Herbaut, Mickael; Baralle, Manon; Lambertyn, Virginie; Rakotoarivonina, Harivoni; Rémond, Caroline; Sarazin, Catherine

2018-03-01

Sequential and simultaneous strategies for fractioning wheat straw were developed in combining 1-ethyl-3-methyl imidazolium acetate [C2mim][OAc], endo-xylanases from Thermobacillus xylanilyticus and commercial cellulases. After [C2mim][OAc]-pretreatment, hydrolysis catalyzed by endo-xylanases of wheat straw led to efficient xylose production with very competitive yield (97.6 ± 1.3%). Subsequent enzymatic saccharification allowed achieving a total degradation of cellulosic fraction (>99%). These high performances revealed an interesting complementarity of [C2mim][OAc]- and xylanase-pretreatments for increasing enzymatic digestibility of cellulosic fraction in agreement with the structural and morphological changes of wheat straw induced by each of these pretreatment steps. In addition a higher tolerance of endo-xylanases from T. xylaniliticus to [C2mim][AcO] until 30% v/v than cellulases from T. reesei was observed. Based on this property, a simultaneous strategy combining [C2mim][OAc]- and endo-xylanases as pretreatment in a one-batch produced xylose with similar yield than those obtained by the sequential strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

The development of CotA mediator cocktail system for dyes decolorization.

PubMed

Luo, S; Xie, T; Liu, Z; Sun, F; Wang, G

2018-05-01

The increasing use of dyes leads to serious environmental concerns, it is significant to explore eco-friendly and economic approaches for dye decolorization. This study aimed to develop mediator cocktail (AS and ABTS) for enhancing the capability of laccase-mediator system in the removal of dyes. By mediator screening, the mediators of ABTS and AS (ABTS, 2, 2'-azino-bis-(3-ethylbenzothiazo-thiazoline-6-sulphonic acid); AS, acetosyringone) were combined for dyes decolorization. The Box-Behnken Design and response surface analysis was performed to optimize experiment conditions. Comparing the CotA-ABTS-AS cocktail system with CotA-single mediator system showed that the coupling of ABTS and AS could increase the decolorization rate 15 times higher, save a third of the cost and shorten the reaction time by 50%. In addition, our studies revealed that sequential oxidation may occur in CotA-ABTS-AS system. Compared with CotA laccase-single mediator system, the CotA-ABTS-AS cocktail system showed advantages including higher efficiency, lower cost and shorter reaction time. This was the first report on the dyes decolorization by laccase mediator cocktail system. These results paved the curb for the application of laccase mediator system in various industrial processes. © 2018 The Society for Applied Microbiology.

Molecular lego for the assembly of biosensing layers.

PubMed

Mano, N; Kuhn, A

2005-03-31

We propose a procedure to assemble monolayers of redox mediator, coenzyme, enzyme and stabilizing polyelectrolyte on an electrode surface using essentially electrostatic and complexing interactions. In a first step a monolayer of redox mediator, substituted nitrofluorenones, is adsorbed. In a second step, a layer of calcium cations is immobilized at the interface. It establishes a bridge between the redox mediator and the subsequently adsorbed coenzyme NAD(+). In the next step we use the intrinsic affinity of the NAD(+) monolayer for dehydrogenases to build up a multilayer composed of mediator/Ca(2+)/NAD(+)/dehydrogenase. The so obtained modified electrode can be used as a biosensor. Quartz crystal microbalance measurements allowed us to better understand the different parameters responsible for the adsorption. A more detailed investigation of the system made it possible to finally stabilize the assembly sufficiently by the adsorption of a polyelectrolyte layer in order to perform rotating disk electrode measurements with the whole supramolecular architecture on the electrode surface.

Patients with Parkinson's Disease Learn to Control Complex Systems via Procedural as Well as Non-Procedural Learning

ERIC Educational Resources Information Center

Osman, Magda; Wilkinson, Leonora; Beigi, Mazda; Castaneda, Cristina Sanchez; Jahanshahi, Marjan

2008-01-01

The striatum is considered to mediate some forms of procedural learning. Complex dynamic control (CDC) tasks involve an individual having to make a series of sequential decisions to achieve a specific outcome (e.g. learning to operate and control a car), and they involve procedural learning. The aim of this study was to test the hypothesis that…

The Longitudinal Effects of Network Characteristics on the Mental Health of Mothers of Children with ASD: The Mediating Role of Parent Cognitions

ERIC Educational Resources Information Center

Benson, Paul R.

2016-01-01

Employing a cohort sequential design, the effects of network characteristics on maternal cognitions (perceived social support and parenting self-efficacy) and mental health (depression and well-being) were assessed over 7 years when children with ASD of mothers in the study were age 7-14. Findings indicated that network size, network emotional…

Pure Red Cell Aplasia After Chemotherapy for Hodgkin’s Lymphoma: In Vitro Evidence for T Cell Mediated Suppression of Erythropoiesis and Response to Sequential Cyclosporin and Erythropoietin

DTIC Science & Technology

1994-01-01

serologies revealed no evidence of recent or active parvovirus , hepatitis A, B, C, or Immunophenotyping studies on peripheral blood lym- Epstein-Barr...impair erythropoietin production in humans [27-291 and Norbert Frickhofer for the B 19 parvovirus studies and in mice [301. As was documented

Relationships among race, education, criminal thinking, and recidivism: moderator and mediator effects.

PubMed

Walters, Glenn D

2014-02-01

Moderator and mediator relationships linking variables from three different theoretical traditions-race (subcultural theory), education (life-course theory), and criminal thinking (social learning theory)-and recidivism were examined in 1,101 released male federal prison inmates. Preliminary regression analyses indicated that racial status (White, Black, Hispanic) moderated the relationship between criminal thinking, as measured by the General Criminal Thinking (GCT) score of the Psychological Inventory of Criminal Thinking Styles (PICTS), and recidivism. Further analysis, however, revealed that it was not racial status, per se, that moderated the relationship between the PICTS and recidivism, but educational attainment. Whereas the PICTS was largely effective in predicting recidivism in inmates with 12 or more years of education, it was largely ineffective in predicting recidivism in inmates with fewer than 12 years of education. When education and the GCT score were compared as possible mediators of the race-recidivism relationship only the GCT successfully mediated this relationship. Sensitivity testing showed that the GCT mediating effect was moderately robust to violations of the sequential ignorability assumption on which causal mediation analysis rests. Moderator and mediator analyses are potentially important avenues through which theoretical constructs can be integrated and assessment strategies devised.

Aclacinomycin A Sensitizes K562 Chronic Myeloid Leukemia Cells to Imatinib through p38MAPK-Mediated Erythroid Differentiation

PubMed Central

Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

2013-01-01

Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and apoptosis. These results provided a potential management by which ACM might have a crucial impact on increasing sensitivity of CML cells to imatinib in the differentiation therapeutic approaches. PMID:23613979

Aclacinomycin A sensitizes K562 chronic myeloid leukemia cells to imatinib through p38MAPK-mediated erythroid differentiation.

PubMed

Lee, Yueh-Lun; Chen, Chih-Wei; Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

2013-01-01

Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and apoptosis. These results provided a potential management by which ACM might have a crucial impact on increasing sensitivity of CML cells to imatinib in the differentiation therapeutic approaches.

Two-stage anaerobic and post-aerobic mesophilic digestion of sewage sludge: Analysis of process performance and hygienization potential.

PubMed

Tomei, M Concetta; Mosca Angelucci, Domenica; Levantesi, Caterina

2016-03-01

Sequential anaerobic-aerobic digestion has been demonstrated to be effective for enhanced sludge stabilization, in terms of increased solid reduction and improvement of sludge dewaterability. In this study, we propose a modified version of the sequential anaerobic-aerobic digestion process by operating the aerobic step under mesophilic conditions (T=37 °C), in order to improve the aerobic degradation kinetics of soluble and particulate chemical oxygen demand (COD). Process performance has been assessed in terms of "classical parameters" such as volatile solids (VS) removal, biogas production, COD removal, nitrogen species, and polysaccharide and protein fate. The aerobic step was operated under intermittent aeration to achieve nitrogen removal. Aerobic mesophilic conditions consistently increased VS removal, providing 32% additional removal vs. 20% at 20 °C. Similar results were obtained for nitrogen removal, increasing from 64% up to 99% at the higher temperature. Improved sludge dewaterability was also observed with a capillary suction time decrease of ~50% during the mesophilic aerobic step. This finding may be attributable to the decreased protein content in the aerobic digested sludge. The post-aerobic digestion exerted a positive effect on the reduction of microbial indicators while no consistent improvement of hygienization related to the increased temperature was observed. The techno-economic analysis of the proposed digestion layout showed a net cost saving for sludge disposal estimated in the range of 28-35% in comparison to the single-phase anaerobic digestion. Copyright © 2015 Elsevier B.V. All rights reserved.

Padova Charter on personal injury and damage under civil-tort law : Medico-legal guidelines on methods of ascertainment and criteria of evaluation.

PubMed

Ferrara, Santo Davide; Baccino, Eric; Boscolo-Berto, Rafael; Comandè, Giovanni; Domenici, Ranieri; Hernandez-Cueto, Claudio; Gulmen, Mete Korkut; Mendelson, George; Montisci, Massimo; Norelli, Gian Aristide; Pinchi, Vilma; Ranavaya, Mohammed; Shokry, Dina A; Sterzik, Vera; Vermylen, Yvo; Vieira, Duarte Nuno; Viel, Guido; Zoja, Riccardo

2016-01-01

Compensation for personal damage, defined as any pecuniary or non-pecuniary loss causally related to a personal injury under civil-tort law, is strictly based on the local jurisdiction and therefore varies significantly across the world. This manuscript presents the first "International Guidelines on Medico-Legal Methods of Ascertainment and Criteria of Evaluation of Personal Injury and Damage under Civil-Tort Law". This consensus document, which includes a step-by-step illustrated explanation of flow charts articulated in eight sequential steps and a comprehensive description of the ascertainment methodology and the criteria of evaluation, has been developed by an International Working Group composed of juridical and medico-legal experts and adopted as Guidelines by the International Academy of Legal Medicine (IALM).

Stepwise strategy to improve Cervical Cancer Screening Adherence (SCAN-CC): automated text messages, phone calls and face-to-face interviews: protocol of a population-based randomised controlled trial.

PubMed

Firmino-Machado, João; Mendes, Romeu; Moreira, Amélia; Lunet, Nuno

2017-10-05

Screening is highly effective for cervical cancer prevention and control. Population-based screening programmes are widely implemented in high-income countries, although adherence is often low. In Portugal, just over half of the women adhere to cervical cancer screening, contributing for greater mortality rates than in other European countries. The most effective adherence raising strategies are based on patient reminders, small/mass media and face-to-face educational programmes, but sequential interventions targeting the general population have seldom been evaluated. The aim of this study is to assess the effectiveness of a stepwise approach, with increasing complexity and cost, to improve adherence to organised cervical cancer screening: step 1a-customised text message invitation; step 1b-customised automated phone call invitation; step 2-secretary phone call; step 3-family health professional phone call and face-to-face appointment. A population-based randomised controlled trial will be implemented in Portuguese urban and rural areas. Women eligible for cervical cancer screening will be randomised (1:1) to intervention and control. In the intervention group, women will be invited for screening through text messages, automated phone calls, manual phone calls and health professional appointments, to be applied sequentially to participants remaining non-adherent after each step. Control will be the standard of care (written letter). The primary outcome is the proportion of women adherent to screening after step 1 or sequences of steps from 1 to 3. The secondary outcomes are: proportion of women screened after each step (1a, 2 and 3); proportion of text messages/phone calls delivered; proportion of women previously screened in a private health institution who change to organised screening. The intervention and control groups will be compared based on intention-to-treat and per-protocol analyses. The study was approved by the Ethics Committee of the Northern Health Region Administration and National Data Protection Committee. Results will be disseminated through communications in scientific meetings and peer-reviewed journals. NCT03122275. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Two-Step Optimization for Spatial Accessibility Improvement: A Case Study of Health Care Planning in Rural China

PubMed Central

Luo, Jing; Tian, Lingling; Luo, Lei; Yi, Hong

2017-01-01

A recent advancement in location-allocation modeling formulates a two-step approach to a new problem of minimizing disparity of spatial accessibility. Our field work in a health care planning project in a rural county in China indicated that residents valued distance or travel time from the nearest hospital foremost and then considered quality of care including less waiting time as a secondary desirability. Based on the case study, this paper further clarifies the sequential decision-making approach, termed “two-step optimization for spatial accessibility improvement (2SO4SAI).” The first step is to find the best locations to site new facilities by emphasizing accessibility as proximity to the nearest facilities with several alternative objectives under consideration. The second step adjusts the capacities of facilities for minimal inequality in accessibility, where the measure of accessibility accounts for the match ratio of supply and demand and complex spatial interaction between them. The case study illustrates how the two-step optimization method improves both aspects of spatial accessibility for health care access in rural China. PMID:28484707

Two-Step Optimization for Spatial Accessibility Improvement: A Case Study of Health Care Planning in Rural China.

PubMed

Luo, Jing; Tian, Lingling; Luo, Lei; Yi, Hong; Wang, Fahui

2017-01-01

A recent advancement in location-allocation modeling formulates a two-step approach to a new problem of minimizing disparity of spatial accessibility. Our field work in a health care planning project in a rural county in China indicated that residents valued distance or travel time from the nearest hospital foremost and then considered quality of care including less waiting time as a secondary desirability. Based on the case study, this paper further clarifies the sequential decision-making approach, termed "two-step optimization for spatial accessibility improvement (2SO4SAI)." The first step is to find the best locations to site new facilities by emphasizing accessibility as proximity to the nearest facilities with several alternative objectives under consideration. The second step adjusts the capacities of facilities for minimal inequality in accessibility, where the measure of accessibility accounts for the match ratio of supply and demand and complex spatial interaction between them. The case study illustrates how the two-step optimization method improves both aspects of spatial accessibility for health care access in rural China.

Simulation of materials processing: Fantasy or reality?

NASA Technical Reports Server (NTRS)

Jenkins, Thomas J.; Bright, Victor M.

1994-01-01

This experiment introduces students to the application of computer-aided design (CAD) and analysis of materials processing in the context of integrated circuit (IC) fabrication. The fabrication of modern IC's is a complex process which consists of several sequential steps. These steps involve the precise control of processing variables such as temperature, humidity, and ambient gas composition. In essence, the particular process employed during the fabrication becomes a 'recipe'. Due to economic and other considerations, CAD is becoming an indispensable part of the development of new recipes for IC fabrication. In particular, this experiment permits the students to explore the CAD of the thermal oxidation of silicon.

Direct C-H Arylation Meets Perovskite Solar Cells: Sn-Free Synthesis Shortcut to High Performance Hole-Transporting Materials.

PubMed

Chang, Yu-Chieh; Lee, Kun-Mu; Lai, Chia-Hsin; Liu, Ching-Yuan

2018-03-30

In contrast to the traditional multistep synthesis, we demonstrate herein a two-step synthesis-shortcut to triphenylamine-based hole-transporting materials (HTMs) through sequential direct C-H arylations. These hole-transporting molecules are fabricated in perovskite-based solar cells (PSCs), exhibiting promising efficiencies up to 17.69%, which is comparable to PSCs utilizing the commercially available spiro-OMeTAD as HTM. This is the first report describing the use of step-saving C-H activations/arylations in the facile synthesis of small-molecule HTMs for perovskite solar cells. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

When the test of mediation is more powerful than the test of the total effect.

PubMed

O'Rourke, Holly P; MacKinnon, David P

2015-06-01

Although previous research has studied power in mediation models, the extent to which the inclusion of a mediator will increase power has not been investigated. To address this deficit, in a first study we compared the analytical power values of the mediated effect and the total effect in a single-mediator model, to identify the situations in which the inclusion of one mediator increased statistical power. The results from this first study indicated that including a mediator increased statistical power in small samples with large coefficients and in large samples with small coefficients, and when coefficients were nonzero and equal across models. Next, we identified conditions under which power was greater for the test of the total mediated effect than for the test of the total effect in the parallel two-mediator model. These results indicated that including two mediators increased power in small samples with large coefficients and in large samples with small coefficients, the same pattern of results that had been found in the first study. Finally, we assessed the analytical power for a sequential (three-path) two-mediator model and compared the power to detect the three-path mediated effect to the power to detect both the test of the total effect and the test of the mediated effect for the single-mediator model. The results indicated that the three-path mediated effect had more power than the mediated effect from the single-mediator model and the test of the total effect. Practical implications of these results for researchers are then discussed.

Isostrychnine synthesis mediated by hypervalent iodine reagent.

PubMed

Jacquemot, Guillaume; Maertens, Gaëtan; Canesi, Sylvain

2015-05-18

Althought there are several reported synthetic routes to strychnine, one of the most widely recognized alkaloids, we report an unexplored route with an oxidative dearomatizing process mediated by hypervalent iodine as the key step. The new syntheses of isostrychnine and strychnine have been achieved from an readily available phenol in nine and ten steps. In addition to the key step, these syntheses involve an aza Michael-ether-enol tandem transformation, two heck type cyclizations, a reductive isomerization, and a double reductive amination in cascade leading to the alkaloid main core. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Associations of life course socioeconomic position and job stress with carotid intima-media thickness. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Camelo, Lidyane V; Giatti, Luana; Chor, Dóra; Griep, Rosane Härter; Benseñor, Isabela M; Santos, Itamar S; Kawachi, Ichiro; Barreto, Sandhi Maria

2015-09-01

The association between life course socioeconomic position (SEP) and subclinical atherosclerosis is not consistent across studies. Socioeconomic adversities early in life are related to an increased probability of a low occupational grade and more stressful jobs in adulthood. However, the role of job stress in explaining the life course social gradient in subclinical atherosclerosis is unknown. To examine whether life course SEP is associated with carotid intima-media thickness (IMT) and to investigate whether this association is partially mediated by job stress. This study used baseline data (2008-2010) for 8806 current workers from ELSA-Brasil. Maternal education, social class of first occupation and social class of current occupation were used to evaluate childhood, youth and adulthood SEP, respectively. Accumulation of risk across the life course was also evaluated. Job stress was assessed by the Swedish Demand-Control-Support Questionnaire. Directed acyclic graph and linear regression models were used. Low childhood SEP was associated with increased IMT only in women, but low youth and adulthood SEP were associated with higher IMT in both genders. The simultaneous adjustment for all SEP indicators showed that only adulthood SEP continued to be associated with IMT. However, higher IMT values were observed among men and women sequentially exposed to low SEP in more than one period of life. High-strain jobs and low job control were not associated with IMT independent of SEP. Our results support a model of the cumulative effects of exposures to SEP across the life span because the highest IMT values were observed in individuals sequentially exposed to low SEP in more than one period of life. We did not find that job stress explained the association between life course SEP and IMT, suggesting that strategies to address socioeconomic inequalities in CVD should target additional steps beyond reducing job stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Density functional theory mechanistic study of the reduction of CO2 to CH4 catalyzed by an ammonium hydridoborate ion pair: CO2 activation via formation of a formic acid entity.

PubMed

Wen, Mingwei; Huang, Fang; Lu, Gang; Wang, Zhi-Xiang

2013-10-21

Density functional theory computations have been applied to gain insight into the CO2 reduction to CH4 with Et3SiH, catalyzed by ammonium hydridoborate 1 ([TMPH](+)[HB(C6F5)3](-), where TMP = 2,2,6,6-tetramethylpiperidine) and B(C6F5)3. The study shows that CO2 is activated through the concerted transfer of H(δ+) and H(δ-) of 1 to CO2, giving a complex (IM2) with a well-formed HCOOH entity, followed by breaking of the O-H bond of the HCOOH entity to return H(δ+) to TMP, resulting in an intermediate 2 ([TMPH](+)[HC(═O)OB(C6F5)3)](-)), with CO2 being inserted into the B-H bond of 1. However, unlike CO2 insertion into transition-metal hydrides, the direct insertion of CO2 into the B-H bond of 1 is inoperative. The computed CO2 activation mechanism agrees with the experimental synthesis of 2 via reacting HCOOH with TMP/B(C6F5)3. Subsequent to the CO2 activation and B(C6F5)3-mediated hydrosilylation of 2 to regenerate the catalyst (1), giving HC(═O)OSiEt3 (5), three hydride-transfer steps take place, sequentially transferring H(δ-) of Et3SiH to 5 to (Et3SiO)2CH2 (6, the product of the first hydride-transfer step) to Et3SiOCH3 (7, the product of the second hydride-transfer step) and finally resulting in CH4. These hydride transfers are mediated by B(C6F5)3 via two SN2 processes without involving 1. B(C6F5)3 acts as a hydride carrier that, with the assistance of a nucleophilic attack of 5-7, first grabs H(δ-) from Et3SiH (the first SN2 process), giving HB(C6F5)3(-), and then leave H(δ-) of HB(C6F5)3(-) to the electrophilic C center of 5-7 (the second SN2 process). The SN2 processes utilize the electrophilic and nucleophilic characteristics possessed by the hydride acceptors (5-7). The hydride-transfer mechanism is different from that in the CO2 reduction to methanol catalyzed by N-heterocyclic carbene (NHC) and PCP-pincer nickel hydride ([Ni]H), where the characteristic of possessing a C═O double bond of the hydride acceptors is utilized for hydride transfer. The mechanistic differences elucidate why the present system can completely reduce CO2 to CH4, whereas NHC and [Ni]H catalysts can only mediate the reduction of CO2 to [Si]OCH3 and catBOCH3, respectively. Understanding this could help in the development of catalysts for selective CO2 reduction to CH4 or methanol.

Three-step sequential positioning algorithm during sonographic evaluation for appendicitis increases appendiceal visualization rate and reduces CT use.

PubMed

Chang, Stephanie T; Jeffrey, R Brooke; Olcott, Eric W

2014-11-01

The purpose of this article is to examine the rates of appendiceal visualization by sonography, imaging-based diagnoses of appendicitis, and CT use after appendiceal sonography, before and after the introduction of a sonographic algorithm involving sequential changes in patient positioning. We used a search engine to retrospectively identify patients who underwent graded-compression sonography for suspected appendicitis during 6-month periods before (period 1; 419 patients) and after (period 2; 486 patients) implementation of a new three-step positional sonographic algorithm. The new algorithm included initial conventional supine scanning and, as long as the appendix remained nonvisualized, left posterior oblique scanning and then "second-look" supine scanning. Abdominal CT within 7 days after sonography was recorded. Between periods 1 and 2, appendiceal visualization on sonography increased from 31.0% to 52.5% (p < 0.001), postsonography CT use decreased from 31.3% to 17.7% (p < 0.001), and the proportion of imaging-based diagnoses of appendicitis made by sonography increased from 63.8% to 85.7% (p = 0.002). The incidence of appendicitis diagnosed by imaging (either sonography or CT) remained similar at 16.5% and 17.3%, respectively (p = 0.790). Sensitivity and overall accuracy were 57.8% (95% CI, 44.8-70.1%) and 93.0% (95% CI, 90.1-95.3%), respectively, in period 1 and 76.5% (95% CI, 65.8-85.2%) and 95.4% (95% CI, 93.1-97.1%), respectively, in period 2. Similar findings were observed for adults and children. Implementation of an ultrasound algorithm with sequential positioning significantly improved the appendiceal visualization rate and the proportion of imaging-based diagnoses of appendicitis made by ultrasound, enabling a concomitant decrease in abdominal CT use in both children and adults.

Risk assessment of trace metals in an extreme environment sediment: shallow, hypersaline, alkaline, and industrial Lake Acıgöl, Denizli, Turkey.

PubMed

Budakoglu, Murat; Karaman, Muhittin; Kumral, Mustafa; Zeytuncu, Bihter; Doner, Zeynep; Yildirim, Demet Kiran; Taşdelen, Suat; Bülbül, Ali; Gumus, Lokman

2018-02-23

The major and trace element component of 48 recent sediment samples in three distinct intervals (0-10, 10-20, and 20-30 cm) from Lake Acıgöl is described to present the current contamination levels and grift structure of detrital and evaporate mineral patterns of these sediments in this extreme saline environment. The spatial and vertical concentrations of major oxides were not uniform in the each subsurface interval. However, similar spatial distribution patterns were observed for some major element couples, due mainly to the detrital and evaporate origin of these elements. A sequential extraction procedure including five distinct steps was also performed to determine the different bonds of trace elements in the < 60-μ particulate size of recent sediments. Eleven trace elements (Ni, Fe, Cd, Pb, Cu, Zn, As, Co, Cr, Al and Mn) in nine surface and subsurface sediment samples were analyzed with chemical partitioning procedures to determine the trace element percentage loads in these different sequential extraction phases. The obtained accuracy values via comparison of the bulk trace metal loads with the total loads of five extraction steps were satisfying for the Ni, Fe, Cd, Zn, and Co. While, bulk analysis results of the Cu, Ni, and V elements have good correlation with total organic matter, organic fraction of sequential extraction characterized by Cu, As, Cd, and Pb. Shallow Lake Acıgöl sediment is characteristic with two different redox layer a) oxic upper level sediments, where trace metals are mobilized, b) reduced subsurface level, where the trace metals are precipitated.

Modeling Search Behaviors during the Acquisition of Expertise in a Sequential Decision-Making Task.

PubMed

Moënne-Loccoz, Cristóbal; Vergara, Rodrigo C; López, Vladimir; Mery, Domingo; Cosmelli, Diego

2017-01-01

Our daily interaction with the world is plagued of situations in which we develop expertise through self-motivated repetition of the same task. In many of these interactions, and especially when dealing with computer and machine interfaces, we must deal with sequences of decisions and actions. For instance, when drawing cash from an ATM machine, choices are presented in a step-by-step fashion and a specific sequence of choices must be performed in order to produce the expected outcome. But, as we become experts in the use of such interfaces, is it possible to identify specific search and learning strategies? And if so, can we use this information to predict future actions? In addition to better understanding the cognitive processes underlying sequential decision making, this could allow building adaptive interfaces that can facilitate interaction at different moments of the learning curve. Here we tackle the question of modeling sequential decision-making behavior in a simple human-computer interface that instantiates a 4-level binary decision tree (BDT) task. We record behavioral data from voluntary participants while they attempt to solve the task. Using a Hidden Markov Model-based approach that capitalizes on the hierarchical structure of behavior, we then model their performance during the interaction. Our results show that partitioning the problem space into a small set of hierarchically related stereotyped strategies can potentially capture a host of individual decision making policies. This allows us to follow how participants learn and develop expertise in the use of the interface. Moreover, using a Mixture of Experts based on these stereotyped strategies, the model is able to predict the behavior of participants that master the task.

An enzymatically-sensitized sequential and concentric energy transfer relay self-assembled around semiconductor quantum dots

NASA Astrophysics Data System (ADS)

Samanta, Anirban; Walper, Scott A.; Susumu, Kimihiro; Dwyer, Chris L.; Medintz, Igor L.

2015-04-01

The ability to control light energy within de novo nanoscale structures and devices will greatly benefit their continuing development and ultimate application. Ideally, this control should extend from generating the light itself to its spatial propagation within the device along with providing defined emission wavelength(s), all in a stand-alone modality. Here we design and characterize macromolecular nanoassemblies consisting of semiconductor quantum dots (QDs), several differentially dye-labeled peptides and the enzyme luciferase which cumulatively demonstrate many of these capabilities by engaging in multiple-sequential energy transfer steps. To create these structures, recombinantly-expressed luciferase and the dye-labeled peptides were appended with a terminal polyhistidine sequence allowing for controlled ratiometric self-assembly around the QDs via metal-affinity coordination. The QDs serve to provide multiple roles in these structures including as central assembly platforms or nanoscaffolds along with acting as a potent energy harvesting and transfer relay. The devices are activated by addition of coelenterazine H substrate which is oxidized by luciferase producing light energy which sensitizes the central 625 nm emitting QD acceptor by bioluminescence resonance energy transfer (BRET). The sensitized QD, in turn, acts as a relay and transfers the energy to a first peptide-labeled Alexa Fluor 647 acceptor dye displayed on its surface. This dye then transfers energy to a second red-shifted peptide-labeled dye acceptor on the QD surface through a second concentric Förster resonance energy transfer (FRET) process. Alexa Fluor 700 and Cy5.5 are both tested in the role of this terminal FRET acceptor. Photophysical analysis of spectral profiles from the resulting sequential BRET-FRET-FRET processes allow us to estimate the efficiency of each of the transfer steps. Importantly, the efficiency of each step within this energy transfer cascade can be controlled to some extent by the number of enzymes/peptides displayed on the QD. Further optimization of the energy transfer process(es) along with potential applications of such devices are finally discussed.The ability to control light energy within de novo nanoscale structures and devices will greatly benefit their continuing development and ultimate application. Ideally, this control should extend from generating the light itself to its spatial propagation within the device along with providing defined emission wavelength(s), all in a stand-alone modality. Here we design and characterize macromolecular nanoassemblies consisting of semiconductor quantum dots (QDs), several differentially dye-labeled peptides and the enzyme luciferase which cumulatively demonstrate many of these capabilities by engaging in multiple-sequential energy transfer steps. To create these structures, recombinantly-expressed luciferase and the dye-labeled peptides were appended with a terminal polyhistidine sequence allowing for controlled ratiometric self-assembly around the QDs via metal-affinity coordination. The QDs serve to provide multiple roles in these structures including as central assembly platforms or nanoscaffolds along with acting as a potent energy harvesting and transfer relay. The devices are activated by addition of coelenterazine H substrate which is oxidized by luciferase producing light energy which sensitizes the central 625 nm emitting QD acceptor by bioluminescence resonance energy transfer (BRET). The sensitized QD, in turn, acts as a relay and transfers the energy to a first peptide-labeled Alexa Fluor 647 acceptor dye displayed on its surface. This dye then transfers energy to a second red-shifted peptide-labeled dye acceptor on the QD surface through a second concentric Förster resonance energy transfer (FRET) process. Alexa Fluor 700 and Cy5.5 are both tested in the role of this terminal FRET acceptor. Photophysical analysis of spectral profiles from the resulting sequential BRET-FRET-FRET processes allow us to estimate the efficiency of each of the transfer steps. Importantly, the efficiency of each step within this energy transfer cascade can be controlled to some extent by the number of enzymes/peptides displayed on the QD. Further optimization of the energy transfer process(es) along with potential applications of such devices are finally discussed. Electronic supplementary information (ESI) available: This material includes control experimental data and select deconvoluted spectra. See DOI: 10.1039/c5nr00828j

Military Review Volume 73 April 1993 Number 4

DTIC Science & Technology

1993-04-01

93--4 Brigadier General Wiliam M. Steele CONTENTS De "ut Commanidant, US4CGSC Military Review Staff 2 Going Deep: Division Air Assault Operations...rotary- Schwarzkopf anmong them, consider the ( obra winged warhorses by the dozen, more than a operation and its agyressive, determined exploi- hundred...rowed. But unquestionably, the capability is through three important, sequential steps: de - there to be used. ciding, battlefield preparations and

Modular synthesis of a dual metal-dual semiconductor nano-heterostructure

DOE PAGES

Amirav, Lilac; Oba, Fadekemi; Aloni, Shaul; ...

2015-04-29

Reported is the design and modular synthesis of a dual metal-dual semiconductor heterostructure with control over the dimensions and placement of its individual components. Analogous to molecular synthesis, colloidal synthesis is now evolving into a series of sequential synthetic procedures with separately optimized steps. Here we detail the challenges and parameters that must be considered when assembling such a multicomponent nanoparticle, and their solutions.

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones

PubMed Central

Linares-Clemente, Pedro; Rozas, José L; Mircheski, Josif; García-Junco-Clemente, Pablo; Martínez-López, José A; Nieto-González, José L; Vázquez, M Eugenio; Pintado, C Oscar; Fernández-Chacón, Rafael

2015-01-01

Key points Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin–phospholipid interaction. Abstract Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB. PMID:25981717

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones.

PubMed

Linares-Clemente, Pedro; Rozas, José L; Mircheski, Josif; García-Junco-Clemente, Pablo; Martínez-López, José A; Nieto-González, José L; Vázquez, M Eugenio; Pintado, C Oscar; Fernández-Chacón, Rafael

2015-07-01

Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin-phospholipid interaction. Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Abscisic acid promotes proteasome-mediated degradation of the transcription coactivator NPR1 in Arabidopsis thaliana.

PubMed

Ding, Yezhang; Dommel, Matthew; Mou, Zhonglin

2016-04-01

Proteasome-mediated turnover of the transcription coactivator NPR1 is pivotal for efficient activation of the broad-spectrum plant immune responses known as localized acquired resistance (LAR) and systemic acquired resistance (SAR) in adjacent and systemic tissues, respectively, and requires the CUL3-based E3 ligase and its adaptor proteins, NPR3 and NPR4, which are receptors for the signaling molecule salicylic acid (SA). It has been shown that SA prevents NPR1 turnover under non-inducing and LAR/SAR-inducing conditions, but how cellular NPR1 homeostasis is maintained remains unclear. Here, we show that the phytohormone abscisic acid (ABA) and SA antagonistically influence cellular NPR1 protein levels. ABA promotes NPR1 degradation via the CUL3(NPR) (3/) (NPR) (4) complex-mediated proteasome pathway, whereas SA may protect NPR1 from ABA-promoted degradation through phosphorylation. Furthermore, we demonstrate that the timing and strength of SA and ABA signaling are critical in modulating NPR1 accumulation and target gene expression. Perturbing ABA or SA signaling in adjacent tissues alters the temporal dynamic pattern of NPR1 accumulation and target gene transcription. Finally, we show that sequential SA and ABA treatment leads to dynamic changes in NPR1 protein levels and target gene expression. Our results revealed a tight correlation between sequential SA and ABA signaling and dynamic changes in NPR1 protein levels and NPR1-dependent transcription in plant immune responses. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Relevance of the Axis Spermidine/eIF5A for Plant Growth and Development

PubMed Central

Belda-Palazón, Borja; Almendáriz, Carla; Martí, Esmeralda; Carbonell, Juan; Ferrando, Alejandro

2016-01-01

One key role of the essential polyamine spermidine in eukaryotes is to provide the 4-aminobutyl moiety group destined to the post-translational modification of a lysine in the highly conserved translation factor eIF5A. This modification is catalyzed by two sequential enzymatic steps leading to the activation of eIF5A by the conversion of one conserved lysine to the unusual amino acid hypusine. The active translation factor facilitates the sequence-specific translation of polyproline sequences that otherwise cause ribosome stalling. In spite of the well-characterized involvement of active eIF5A in the translation of proline repeat-rich proteins, its biological role has been recently elucidated only in mammals, and it is poorly described at the functional level in plants. Here we describe the alterations in plant growth and development caused by RNAi-mediated conditional genetic inactivation of the hypusination pathway in Arabidopsis thaliana by knocking-down the enzyme deoxyhypusine synthase. We have uncovered that spermidine-mediated activation of eIF5A by hypusination is involved in several aspects of plant biology such as the control of flowering time, the aerial and root architecture, and root hair growth. In addition this pathway is required for adaptation to challenging growth conditions such as high salt and high glucose medium and to elevated concentrations of the plant hormone ABA. We have also performed a bioinformatic analysis of polyproline-rich containing proteins as putative eIF5A targets to uncover their organization in clusters of protein networks to find molecular culprits for the disclosed phenotypes. This study represents a first attempt to provide a holistic view of the biological relevance of the spermidine-dependent hypusination pathway for plant growth and development. PMID:26973686

Temporal course of gene expression during motor memory formation in primary motor cortex of rats.

PubMed

Hertler, B; Buitrago, M M; Luft, A R; Hosp, J A

2016-12-01

Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that depends on changes in gene expression. Here, we investigate the temporal profile of these changes during motor memory formation in response to a skilled reaching task in rats. mRNA-levels were measured 1h, 7h and 24h after the end of a training session using microarray technique. To assure learning specificity, trained animals were compared to a control group. In response to motor learning, genes are sequentially regulated with high time-point specificity and a shift from initial suppression to later activation. The majority of regulated genes can be linked to learning-related plasticity. In the gene-expression cascade following motor learning, three different steps can be defined: (1) an initial suppression of genes influencing gene transcription. (2) Expression of genes that support translation of mRNA in defined compartments. (3) Expression of genes that immediately mediates plastic changes. Gene expression peaks after 24h - this is a much slower time-course when compared to hippocampus-dependent learning, where peaks of gene-expression can be observed 6-12h after training ended. Copyright © 2016 Elsevier Inc. All rights reserved.

Recycling Endosomes and Viral Infection.

PubMed

Vale-Costa, Sílvia; Amorim, Maria João

2016-03-08

Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral-host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition.

The Effect of Basepair Mismatch on DNA Strand Displacement.

PubMed

Broadwater, D W Bo; Kim, Harold D

2016-04-12

DNA strand displacement is a key reaction in DNA homologous recombination and DNA mismatch repair and is also heavily utilized in DNA-based computation and locomotion. Despite its ubiquity in science and engineering, sequence-dependent effects of displacement kinetics have not been extensively characterized. Here, we measured toehold-mediated strand displacement kinetics using single-molecule fluorescence in the presence of a single basepair mismatch. The apparent displacement rate varied significantly when the mismatch was introduced in the invading DNA strand. The rate generally decreased as the mismatch in the invader was encountered earlier in displacement. Our data indicate that a single base pair mismatch in the invader stalls branch migration and displacement occurs via direct dissociation of the destabilized incumbent strand from the substrate strand. We combined both branch migration and direct dissociation into a model, which we term the concurrent displacement model, and used the first passage time approach to quantitatively explain the salient features of the observed relationship. We also introduce the concept of splitting probabilities to justify that the concurrent model can be simplified into a three-step sequential model in the presence of an invader mismatch. We expect our model to become a powerful tool to design DNA-based reaction schemes with broad functionality. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Recycling Endosomes and Viral Infection

PubMed Central

Vale-Costa, Sílvia; Amorim, Maria João

2016-01-01

Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral–host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition. PMID:27005655

[Markerless DNA deletion based on Red recombination and in vivo I-Sec I endonuclease cleavage in Escherichia coli chromosome].

PubMed

Zhu, Meiqin; Yu, Jian; Zhou, Changlin; Fang, Hongqing

2016-01-01

Red-based recombineering has been widely used in Escherichia coli genome modification through electroporating PCR fragments into electrocompetent cells to replace target sequences. Some mutations in the PCR fragments may be brought into the homologous regions near the target. To solve this problem in markeless gene deletion we developed a novel method characterized with two-step recombination and a donor plasmid. First, generated by PCR a linear DNA cassette which comprises a I-Sec I site-containing marker gene and homologous arms was electroporated into cells for marker-substitution deletion of the target sequence. Second, after a donor plasmid carrying the I-Sec I site-containing fusion homologous arm was chemically transformed into the marker-containing cells, the fusion arms and the marker was simultaneously cleaved by I-Sec I endonuclease and the marker-free deletion was stimulated by double-strand break-mediated intermolecular recombination. Eleven nonessential regions in E. coli DH1 genome were sequentially deleted by our method, resulting in a 10.59% reduced genome size. These precise deletions were also verified by PCR sequencing and genome resequencing. Though no change in the growth rate on the minimal medium, we found the genome-reduced strains have some alteration in the acid resistance and for the synthesis of lycopene.

Does the Menstrual Cycle Influence the Sensitivity of Vagally Mediated Baroreflexes?

DTIC Science & Technology

2002-06-01

the study. Baroreflex measurements We applied sequential neck pressure and suction to modulate carotid baroreceptors , and recorded the re- sulting...the day menses began was designated day 0). At the beginning of each data collection period, sphygmomanometric blood pressures were re- corded with...between arterial pressure and R-R interval, suggesting that high levels of sympathetic nervous activity or of plasma noradrenaline may override or inhibit

A Novel System for Simultaneous or Sequential Integration of Multiple Gene-Loading Vectors into a Defined Site of a Human Artificial Chromosome

PubMed Central

Suzuki, Teruhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo; Hara, Takahiko

2014-01-01

Human artificial chromosomes (HACs) are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV) into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system) via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming. PMID:25303219

A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome.

PubMed

Suzuki, Teruhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo; Hara, Takahiko

2014-01-01

Human artificial chromosomes (HACs) are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV) into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system) via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming.

Where are we coming from versus who we will become: the effect of priming different contents of European identity on cooperation.

PubMed

La Barbera, Francesco; Ferrara, Pia Cariota; Boza, Mihaela

2014-12-01

In two experiments, we investigated how priming European identity as common project versus common heritage affects participants' cooperation in a social dilemma; an additional aim was to explore the mediators involved in the process. In the first experiment, 82 students played a public good dilemma with a European bogus partner and then completed self-report measures of identification with the European Union (EU), group-based trust and collective interest. Results showed that priming a common project-based but not a common heritage-based European social identity fostered cooperative behaviour; this effect was mediated by two sequential mediators: the common project prime increased participants' strength of identification with EU (mediator 1) which, in turn, positively affected group-based trust (mediator 2), fostering greater cooperation. Experiment 2 was conducted with a similar procedure on a sample of 124 students, using a different measure of trust and changing the order of mediators. Results supported those of previous experiment: Priming a project-based EU identity content (compared to heritage-based one) had significant direct and indirect effects on cooperation. © 2014 International Union of Psychological Science.

Identity-level representations affect unfamiliar face matching performance in sequential but not simultaneous tasks.

PubMed

Menon, Nadia; White, David; Kemp, Richard I

2015-01-01

According to cognitive and neurological models of the face-processing system, faces are represented at two levels of abstraction. First, image-based pictorial representations code a particular instance of a face and include information that is unrelated to identity-such as lighting, pose, and expression. Second, at a more abstract level, identity-specific representations combine information from various encounters with a single face. Here we tested whether identity-level representations mediate unfamiliar face matching performance. Across three experiments we manipulated identity attributions to pairs of target images and measured the effect on subsequent identification decisions. Participants were instructed that target images were either two photos of the same person (1ID condition) or photos of two different people (2ID condition). This manipulation consistently affected performance in sequential matching: 1ID instructions improved accuracy on "match" trials and caused participants to adopt a more liberal response bias than the 2ID condition. However, this manipulation did not affect performance in simultaneous matching. We conclude that identity-level representations, generated in working memory, influence the amount of variation tolerated between images, when making identity judgements in sequential face matching.

Sequential stages and distribution patterns of aging-related tau astrogliopathy (ARTAG) in the human brain.

PubMed

Kovacs, Gabor G; Xie, Sharon X; Robinson, John L; Lee, Edward B; Smith, Douglas H; Schuck, Theresa; Lee, Virginia M-Y; Trojanowski, John Q

2018-06-11

Aging-related tau astrogliopathy (ARTAG) describes tau pathology in astrocytes in different locations and anatomical regions. In the present study we addressed the question of whether sequential distribution patterns can be recognized for ARTAG or astroglial tau pathologies in both primary FTLD-tauopathies and non-FTLD-tauopathy cases. By evaluating 687 postmortem brains with diverse disorders we identified ARTAG in 455. We evaluated frequencies and hierarchical clustering of anatomical involvement and used conditional probability and logistic regression to model the sequential distribution of ARTAG and astroglial tau pathologies across different brain regions. For subpial and white matter ARTAG we recognize three and two patterns, respectively, each with three stages initiated or ending in the amygdala. Subependymal ARTAG does not show a clear sequential pattern. For grey matter (GM) ARTAG we recognize four stages including a striatal pathway of spreading towards the cortex and/or amygdala, and the brainstem, and an amygdala pathway, which precedes the involvement of the striatum and/or cortex and proceeds towards the brainstem. GM ARTAG and astrocytic plaque pathology in corticobasal degeneration follows a predominantly frontal-parietal cortical to temporal-occipital cortical, to subcortical, to brainstem pathway (four stages). GM ARTAG and tufted astrocyte pathology in progressive supranuclear palsy shows a striatum to frontal-parietal cortical to temporal to occipital, to amygdala, and to brainstem sequence (four stages). In Pick's disease cases with astroglial tau pathology an overlapping pattern with PSP can be appreciated. We conclude that tau-astrogliopathy type-specific sequential patterns cannot be simplified as neuron-based staging systems. The proposed cytopathological and hierarchical stages provide a conceptual approach to identify the initial steps of the pathogenesis of tau pathologies in ARTAG and primary FTLD-tauopathies.

Testing a stepped care model for binge-eating disorder: a two-step randomized controlled trial.

PubMed

Tasca, Giorgio A; Koszycki, Diana; Brugnera, Agostino; Chyurlia, Livia; Hammond, Nicole; Francis, Kylie; Ritchie, Kerri; Ivanova, Iryna; Proulx, Genevieve; Wilson, Brian; Beaulac, Julie; Bissada, Hany; Beasley, Erin; Mcquaid, Nancy; Grenon, Renee; Fortin-Langelier, Benjamin; Compare, Angelo; Balfour, Louise

2018-05-24

A stepped care approach involves patients first receiving low-intensity treatment followed by higher intensity treatment. This two-step randomized controlled trial investigated the efficacy of a sequential stepped care approach for the psychological treatment of binge-eating disorder (BED). In the first step, all participants with BED (n = 135) received unguided self-help (USH) based on a cognitive-behavioral therapy model. In the second step, participants who remained in the trial were randomized either to 16 weeks of group psychodynamic-interpersonal psychotherapy (GPIP) (n = 39) or to a no-treatment control condition (n = 46). Outcomes were assessed for USH in step 1, and then for step 2 up to 6-months post-treatment using multilevel regression slope discontinuity models. In the first step, USH resulted in large and statistically significant reductions in the frequency of binge eating. Statistically significant moderate to large reductions in eating disorder cognitions were also noted. In the second step, there was no difference in change in frequency of binge eating between GPIP and the control condition. Compared with controls, GPIP resulted in significant and large improvement in attachment avoidance and interpersonal problems. The findings indicated that a second step of a stepped care approach did not significantly reduce binge-eating symptoms beyond the effects of USH alone. The study provided some evidence for the second step potentially to reduce factors known to maintain binge eating in the long run, such as attachment avoidance and interpersonal problems.

Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders

PubMed Central

Goebel-Goody, Susan M.; Baum, Matthew; Paspalas, Constantinos D.; Fernandez, Stephanie M.; Carty, Niki C.; Kurup, Pradeep

2012-01-01

Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase that modulates key signaling molecules involved in synaptic plasticity and neuronal function. Targets include extracellular-regulated kinase 1 and 2 (ERK1/2), stress-activated protein kinase p38 (p38), the Src family tyrosine kinase Fyn, N-methyl-d-aspartate receptors (NMDARs), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). STEP-mediated dephosphorylation of ERK1/2, p38, and Fyn leads to inactivation of these enzymes, whereas STEP-mediated dephosphorylation of surface NMDARs and AMPARs promotes their endocytosis. Accordingly, the current model of STEP function posits that it opposes long-term potentiation and promotes long-term depression. Phosphorylation, cleavage, dimerization, ubiquitination, and local translation all converge to maintain an appropriate balance of STEP in the central nervous system. Accumulating evidence over the past decade indicates that STEP dysregulation contributes to the pathophysiology of several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, fragile X syndrome, epileptogenesis, alcohol-induced memory loss, Huntington's disease, drug abuse, stroke/ischemia, and inflammatory pain. This comprehensive review discusses STEP expression and regulation and highlights how disrupted STEP function contributes to the pathophysiology of diverse neuropsychiatric disorders. PMID:22090472

On the effect of response transformations in sequential parameter optimization.

PubMed

Wagner, Tobias; Wessing, Simon

2012-01-01

Parameter tuning of evolutionary algorithms (EAs) is attracting more and more interest. In particular, the sequential parameter optimization (SPO) framework for the model-assisted tuning of stochastic optimizers has resulted in established parameter tuning algorithms. In this paper, we enhance the SPO framework by introducing transformation steps before the response aggregation and before the actual modeling. Based on design-of-experiments techniques, we empirically analyze the effect of integrating different transformations. We show that in particular, a rank transformation of the responses provides significant improvements. A deeper analysis of the resulting models and additional experiments with adaptive procedures indicates that the rank and the Box-Cox transformation are able to improve the properties of the resultant distributions with respect to symmetry and normality of the residuals. Moreover, model-based effect plots document a higher discriminatory power obtained by the rank transformation.

Parallel solution of closely coupled systems

NASA Technical Reports Server (NTRS)

Utku, S.; Salama, M.

1986-01-01

The odd-even permutation and associated unitary transformations for reordering the matrix coefficient A are employed as means of breaking the strong seriality which is characteristic of closely coupled systems. The nested dissection technique is also reviewed, and the equivalence between reordering A and dissecting its network is established. The effect of transforming A with odd-even permutation on its topology and the topology of its Cholesky factors is discussed. This leads to the construction of directed graphs showing the computational steps required for factoring A, their precedence relationships and their sequential and concurrent assignment to the available processors. Expressions for the speed-up and efficiency of using N processors in parallel relative to the sequential use of a single processor are derived from the directed graph. Similar expressions are also derived when the number of available processors is fewer than required.

Sequential Superresolution Imaging of Multiple Targets Using a Single Fluorophore

PubMed Central

Lidke, Diane S.; Lidke, Keith A.

2015-01-01

Fluorescence superresolution (SR) microscopy, or fluorescence nanoscopy, provides nanometer scale detail of cellular structures and allows for imaging of biological processes at the molecular level. Specific SR imaging methods, such as localization-based imaging, rely on stochastic transitions between on (fluorescent) and off (dark) states of fluorophores. Imaging multiple cellular structures using multi-color imaging is complicated and limited by the differing properties of various organic dyes including their fluorescent state duty cycle, photons per switching event, number of fluorescent cycles before irreversible photobleaching, and overall sensitivity to buffer conditions. In addition, multiple color imaging requires consideration of multiple optical paths or chromatic aberration that can lead to differential aberrations that are important at the nanometer scale. Here, we report a method for sequential labeling and imaging that allows for SR imaging of multiple targets using a single fluorophore with negligible cross-talk between images. Using brightfield image correlation to register and overlay multiple image acquisitions with ~10 nm overlay precision in the x-y imaging plane, we have exploited the optimal properties of AlexaFluor647 for dSTORM to image four distinct cellular proteins. We also visualize the changes in co-localization of the epidermal growth factor (EGF) receptor and clathrin upon EGF addition that are consistent with clathrin-mediated endocytosis. These results are the first to demonstrate sequential SR (s-SR) imaging using direct stochastic reconstruction microscopy (dSTORM), and this method for sequential imaging can be applied to any superresolution technique. PMID:25860558

Sequential programmable self-assembly: Role of cooperative interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jonathan D. Halverson; Tkachenko, Alexei V.

Here, we propose a general strategy of “sequential programmable self-assembly” that enables a bottom-up design of arbitrary multi-particle architectures on nano- and microscales. We show that a naive realization of this scheme, based on the pairwise additive interactions between particles, has fundamental limitations that lead to a relatively high error rate. This can be overcome by using cooperative interparticle binding. The cooperativity is a well known feature of many biochemical processes, responsible, e.g., for signaling and regulations in living systems. Here we propose to utilize a similar strategy for high precision self-assembly, and show that DNA-mediated interactions provide a convenientmore » platform for its implementation. In particular, we outline a specific design of a DNA-based complex which we call “DNA spider,” that acts as a smart interparticle linker and provides a built-in cooperativity of binding. We demonstrate versatility of the sequential self-assembly based on spider-functionalized particles by designing several mesostructures of increasing complexity and simulating their assembly process. This includes a number of finite and repeating structures, in particular, the so-called tetrahelix and its several derivatives. Due to its generality, this approach allows one to design and successfully self-assemble virtually any structure made of a “GEOMAG” magnetic construction toy, out of nanoparticles. According to our results, once the binding cooperativity is strong enough, the sequential self-assembly becomes essentially error-free.« less

Sequential programmable self-assembly: Role of cooperative interactions

DOE PAGES

Jonathan D. Halverson; Tkachenko, Alexei V.

2016-03-04

Here, we propose a general strategy of “sequential programmable self-assembly” that enables a bottom-up design of arbitrary multi-particle architectures on nano- and microscales. We show that a naive realization of this scheme, based on the pairwise additive interactions between particles, has fundamental limitations that lead to a relatively high error rate. This can be overcome by using cooperative interparticle binding. The cooperativity is a well known feature of many biochemical processes, responsible, e.g., for signaling and regulations in living systems. Here we propose to utilize a similar strategy for high precision self-assembly, and show that DNA-mediated interactions provide a convenientmore » platform for its implementation. In particular, we outline a specific design of a DNA-based complex which we call “DNA spider,” that acts as a smart interparticle linker and provides a built-in cooperativity of binding. We demonstrate versatility of the sequential self-assembly based on spider-functionalized particles by designing several mesostructures of increasing complexity and simulating their assembly process. This includes a number of finite and repeating structures, in particular, the so-called tetrahelix and its several derivatives. Due to its generality, this approach allows one to design and successfully self-assemble virtually any structure made of a “GEOMAG” magnetic construction toy, out of nanoparticles. According to our results, once the binding cooperativity is strong enough, the sequential self-assembly becomes essentially error-free.« less

Highly Stable Double-Stranded DNA Containing Sequential Silver(I)-Mediated 7-Deazaadenine/Thymine Watson-Crick Base Pairs.

PubMed

Santamaría-Díaz, Noelia; Méndez-Arriaga, José M; Salas, Juan M; Galindo, Miguel A

2016-05-17

The oligonucleotide d(TX)9 , which consists of an octadecamer sequence with alternating non-canonical 7-deazaadenine (X) and canonical thymine (T) as the nucleobases, was synthesized and shown to hybridize into double-stranded DNA through the formation of hydrogen-bonded Watson-Crick base pairs. dsDNA with metal-mediated base pairs was then obtained by selectively replacing W-C hydrogen bonds by coordination bonds to central silver(I) ions. The oligonucleotide I adopts a duplex structure in the absence of Ag(+) ions, and its stability is significantly enhanced in the presence of Ag(+) ions while its double-helix structure is retained. Temperature-dependent UV spectroscopy, circular dichroism spectroscopy, and ESI mass spectrometry were used to confirm the selective formation of the silver(I)-mediated base pairs. This strategy could become useful for preparing stable metallo-DNA-based nanostructures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Relationship between Job Demands and Employees' Counterproductive Work Behaviors: The Mediating Effect of Psychological Detachment and Job Anxiety.

PubMed

Chen, Yang; Li, Shuang; Xia, Qing; He, Chao

2017-01-01

This study aims to explore the relation between job demands and counterproductive work behaviors (CWBs). A cross-sectional sample of 439 coal miners completed a self-report questionnaire that assessed their job demands, psychological detachment, job anxiety, and CWBs in a Chinese context. The conceptual model, based on the stressor-detachment model, was examined using structural equation modeling. The results suggest that psychological detachment mediates not only the relation between job demands and job anxiety but also that between job demands and CWBs. Furthermore, the relation between job demands and CWBs is sequentially mediated by psychological detachment and job anxiety. Our findings validate the effectiveness of the stressor-detachment model. Moreover, we demonstrate that the underlying mechanism of the relation between job demands and CWBs can be explained by psychological detachment and job anxiety.

Characterization of soluble glycoprotein D-mediated herpes simplex virus type 1 infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsvitov, Marianna; Frampton, Arthur R.; Shah, Waris A.

2007-04-10

Herpes simplex virus type 1 (HSV-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (GAGs) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein D (gD) to cognate receptors. In this study, we characterized the observation that soluble forms of the gD ectodomain (sgD) can mediate entry of gD-deficient HSV-1. We examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to determine the order and stability of the initial interactions required for entry. Surprisingly, virus binding to GAGs did not increase the efficiency of sgD-mediated entry andmore » gD-deficient virus was capable of attaching to GAG-deficient cells in the absence of sgD. These observations suggested a novel binding interaction that may play a role in normal HSV infection.« less

The Relationship between Job Demands and Employees’ Counterproductive Work Behaviors: The Mediating Effect of Psychological Detachment and Job Anxiety

PubMed Central

Chen, Yang; Li, Shuang; Xia, Qing; He, Chao

2017-01-01

This study aims to explore the relation between job demands and counterproductive work behaviors (CWBs). A cross-sectional sample of 439 coal miners completed a self-report questionnaire that assessed their job demands, psychological detachment, job anxiety, and CWBs in a Chinese context. The conceptual model, based on the stressor-detachment model, was examined using structural equation modeling. The results suggest that psychological detachment mediates not only the relation between job demands and job anxiety but also that between job demands and CWBs. Furthermore, the relation between job demands and CWBs is sequentially mediated by psychological detachment and job anxiety. Our findings validate the effectiveness of the stressor-detachment model. Moreover, we demonstrate that the underlying mechanism of the relation between job demands and CWBs can be explained by psychological detachment and job anxiety. PMID:29163274

Nanospace-Mediated Self-Organization of Nanoparticles in Flexible Porous Polymer Templates.

PubMed

Kuroda, Yoshiyuki; Muto, Itaru; Shimojima, Atsushi; Wada, Hiroaki; Kuroda, Kazuyuki

2017-09-12

Self-organization is a fundamental process for the construction of complex hierarchically ordered nanostructures, which are widespread in biological systems. However, precise control of size, shape, and surface properties is required for self-organization of nanoparticles. Here, we demonstrate a novel self-organization phenomenon mediated by flexible nanospaces in templates. Inorganic nanoparticles (e.g., silica, zirconia, and titania) are deposited in porous polymer thin films with randomly distributed pores on the surface, leaving a partially filled nanospace in each pore. Heating at temperatures beyond the glass transition temperature of the template leads to self-organization of the inorganic nanoparticles into one-dimensional chainlike networks. The self-organization is mediated by the deformation and fusion of the residual nanospaces, and it can be rationally controlled by sequential heat treatments. These results show that a nanospace, defined by the nonexistence of matter, interacts indirectly with matter and can be used as a component of self-organization systems.

Promoting safety voice with safety-specific transformational leadership: the mediating role of two dimensions of trust.

PubMed

Conchie, Stacey M; Taylor, Paul J; Donald, Ian J

2012-01-01

Although safety-specific transformational leadership is known to encourage employee safety voice behaviors, less is known about what makes this style of leadership effective. We tested a model that links safety-specific transformational leadership to safety voice through various dimensions of trust. Data from 150 supervisor-employee dyads from the United Kingdom oil industry supported our predictions that the effects of safety-specific transformational leadership are sequentially mediated by affect-based trust beliefs and disclosure trust intentions. Moreover, we found that reliance trust intentions moderated the effect of disclosure: employees' disclosure intentions mediated the effects of affect-based trust on safety voice behaviors only when employees' intention to rely on their leader was moderate to high. These findings suggest that leaders seeking to encourage safety voice behaviors should go beyond "good reason" arguments and develop affective bonds with their employees.

System 2020 - Strategic Initiative

DTIC Science & Technology

2010-08-26

needs  fast,  flexible  and  adaptable  capabilities  (and  tools  that   enable  the   development   of  these...S2020  (and   enabling  acquisition   improvements)   System  Design   and   Development   Speed   Sequential  single-­‐step... development   time   as   a   function   of   SLOC   up   to   1250   KSLOC.

Earth Science and Applications attached payloads on Space Station

NASA Technical Reports Server (NTRS)

Wicks, Thomas G.; Arnold, Ralph R.

1990-01-01

This paper describes the Office of Space Science and Applications' process for Attached Payloads on Space Station Freedom from development through on-orbit operations. Its primary objectives are to detail the sequential steps of the attached payload methodology by tracing in particular the selected Earth Science and Applications' payloads through this flow and relate the integral role of Marshall Space Flight Center's Science Utilization Management function of integration and operations.

Regulation of Corneal Stroma Extracellular Matrix Assembly

PubMed Central

Chen, Shoujun; Mienaltowski, Michael J.; Birk, David E.

2014-01-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. PMID:25819456

Utilization of optimized BCR three-step sequential and dilute HCl single extraction procedures for soil-plant metal transfer predictions in contaminated lands.

PubMed

Kubová, Jana; Matús, Peter; Bujdos, Marek; Hagarová, Ingrid; Medved', Ján

2008-05-30

The prediction of soil metal phytoavailability using the chemical extractions is a conventional approach routinely used in soil testing. The adequacy of such soil tests for this purpose is commonly assessed through a comparison of extraction results with metal contents in relevant plants. In this work, the fractions of selected risk metals (Al, As, Cd, Cu, Fe, Mn, Ni, Pb, Zn) that can be taken up by various plants were obtained by optimized BCR (Community Bureau of Reference) three-step sequential extraction procedure (SEP) and by single 0.5 mol L(-1) HCl extraction. These procedures were validated using five soil and sediment reference materials (SRM 2710, SRM 2711, CRM 483, CRM 701, SRM RTH 912) and applied to significantly different acidified soils for the fractionation of studied metals. The new indicative values of Al, Cd, Cu, Fe, Mn, P, Pb and Zn fractional concentrations for these reference materials were obtained by the dilute HCl single extraction. The influence of various soil genesis, content of essential elements (Ca, Mg, K, P) and different anthropogenic sources of acidification on extraction yields of individual risk metal fractions was investigated. The concentrations of studied elements were determined by atomic spectrometry methods (flame, graphite furnace and hydride generation atomic absorption spectrometry and inductively coupled plasma optical emission spectrometry). It can be concluded that the data of extraction yields from first BCR SEP acid extractable step and soil-plant transfer coefficients can be applied to the prediction of qualitative mobility of selected risk metals in different soil systems.

Effect of reductant and PVP on morphology and magnetic property of ultrafine Ni powders prepared via hydrothermal route

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jun, E-mail: j-zhang@126.com; Wang, Xiucai; Li, Lili

2013-10-15

Graphical abstract: The ultrafine Ni powders with the shapes including sphere, pearl-string, leaf, fish-bone, hexagonal sheet and silknet were prepared through one-step hydrothermal reduction using different reductants. Their saturation magnetization, remanent magnetization and coercivity sequentially increase, and the coercivity of hexagonal sheet-like Ni powders increases by 25% compared with the Ni bulk counterpart. - Highlights: • The ultrafine Ni powders with various shapes of sphere, fish-bone, hexagonal sheet, etc. • Facile and one-step hydrothermal reduction using three reductants and PVP additive was developed. • Magnetic properties of the ultrafine Ni powders with different shapes were measured. • Compared with bulkmore » Ni material, coercivity of hexagonal sheet Ni increases by 25%. • The formation mechanism of the shapes was suggested. - Abstract: The ultrafine nickel particles with different shapes including sphere, pearl-string, leaf, fish-bone, hexagonal sheet and silknet were prepared through one-step hydrothermal reduction using hydrazine hydrate, sodium hypophosphite and ethylene glycol as reductants, polyvinylpyrrolidone as structure-directing agent. It has been verified with the characterization of X-ray powder diffraction and transmission/scanning electronic microscopy that as-prepared products belong to face-centered cubic structure of nickel microcrystals with high purity and fine dispersity. The magnetic hysteresis loops measured at room temperature reveal that the values of saturation magnetization, remanent magnetization and coercivity rise sequentially from silknet, sphere to hexagonal sheet. In comparison with nickel bulk counterpart, the coercivity of the hexagonal sheet nickel powders increases by 25%.« less

Multiple-step relayed correlation spectroscopy: sequential resonance assignments in oligosaccharides.

PubMed Central

Homans, S W; Dwek, R A; Fernandes, D L; Rademacher, T W

1984-01-01

A general property of the high-resolution proton NMR spectra of oligosaccharides is the appearance of low-field well-resolved resonances corresponding to the anomeric (H1) and H2 protons. The remaining skeletal protons resonate in the region 3-4 ppm, giving rise to an envelope of poorly resolved resonances. Assignments can be made from the H1 and H2 protons to their J-coupled neighbors (H2 and H3) within this main envelope by using 1H-1H correlated spectroscopy. However, the tight coupling (J congruent to delta) between further protons results in poor spectral dispersion with consequent assignment ambiguities. We describe here three-step two-dimensional relayed correlation spectroscopy and show how it can be used to correlate the resolved anomeric (H1) and H2 protons with remote (H4, H5) protons directly through a linear network of couplings using sequential magnetization transfer around the oligosaccharide rings. Resonance assignments are then obtained by inspection of cross-peaks that appear in well-resolved regions of the two-dimensional spectrum. This offers a general solution to the assignment problem in oligosaccharides and, importantly, these assignments will subsequently allow for the three-dimensional solution conformation to be determined by using one-dimensional and two-dimensional nuclear Overhauser experiments. PMID:6593701

Sequential double photodetachment of He- in elliptically polarized laser fields

NASA Astrophysics Data System (ADS)

Génévriez, Matthieu; Dunseath, Kevin M.; Terao-Dunseath, Mariko; Urbain, Xavier

2018-02-01

Four-photon double detachment of the helium negative ion is investigated experimentally and theoretically for photon energies where the transient helium atom is in the 1 s 2 s 3S or 1 s 2 p P3o states, which subsequently ionize by absorption of three photons. Ionization is enhanced by intermediate resonances, giving rise to series of peaks in the He+ spectrum, which we study in detail. The He+ yield is measured in the wavelength ranges from 530 to 560 nm and from 685 to 730 nm and for various polarizations of the laser light. Double detachment is treated theoretically as a sequential process, within the framework of R -matrix theory for the first step and effective Hamiltonian theory for the second step. Experimental conditions are accurately modeled, and the measured and simulated yields are in good qualitative and, in some cases, quantitative agreement. Resonances in the double detachment spectra can be attributed to well-defined Rydberg states of the transient atom. The double detachment yield exhibits a strong dependence on the laser polarization which can be related to the magnetic quantum number of the intermediate atomic state. We also investigate the possibility of nonsequential double detachment with a two-color experiment but observe no evidence for it.

Deconvolution of complex differential scanning calorimetry profiles for protein transitions under kinetic control.

PubMed

Toledo-Núñez, Citlali; Vera-Robles, L Iraís; Arroyo-Maya, Izlia J; Hernández-Arana, Andrés

2016-09-15

A frequent outcome in differential scanning calorimetry (DSC) experiments carried out with large proteins is the irreversibility of the observed endothermic effects. In these cases, DSC profiles are analyzed according to methods developed for temperature-induced denaturation transitions occurring under kinetic control. In the one-step irreversible model (native → denatured) the characteristics of the observed single-peaked endotherm depend on the denaturation enthalpy and the temperature dependence of the reaction rate constant, k. Several procedures have been devised to obtain the parameters that determine the variation of k with temperature. Here, we have elaborated on one of these procedures in order to analyze more complex DSC profiles. Synthetic data for a heat capacity curve were generated according to a model with two sequential reactions; the temperature dependence of each of the two rate constants involved was determined, according to the Eyring's equation, by two fixed parameters. It was then shown that our deconvolution procedure, by making use of heat capacity data alone, permits to extract the parameter values that were initially used. Finally, experimental DSC traces showing two and three maxima were analyzed and reproduced with relative success according to two- and four-step sequential models. Copyright © 2016 Elsevier Inc. All rights reserved.

Sequential protein extraction as an efficient method for improved proteome coverage in larvae of Atlantic salmon (Salmo salar).

PubMed

Nuez-Ortín, Waldo G; Carter, Chris G; Nichols, Peter D; Wilson, Richard

2016-07-01

Understanding diet- and environmentally induced physiological changes in fish larvae is a major goal for the aquaculture industry. Proteomic analysis of whole fish larvae comprising multiple tissues offers considerable potential but is challenging due to the very large dynamic range of protein abundance. To extend the coverage of the larval phase of the Atlantic salmon (Salmo salar) proteome, we applied a two-step sequential extraction (SE) method, based on differential protein solubility, using a nondenaturing buffer containing 150 mM NaCl followed by a denaturing buffer containing 7 M urea and 2 M thiourea. Extracts prepared using SE and one-step direct extraction were characterized via label-free shotgun proteomics using nanoLC-MS/MS (LTQ-Orbitrap). SE partitioned the proteins into two fractions of approximately equal amounts, but with very distinct protein composition, leading to identification of ∼40% more proteins than direct extraction. This fractionation strategy enabled the most detailed characterization of the salmon larval proteome to date and provides a platform for greater understanding of physiological changes in whole fish larvae. The MS data are available via the ProteomeXchange Consortium PRIDE partner repository, dataset PXD003366. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Save the last dance for me: unwanted serial position effects in jury evaluations.

PubMed

Bruine de Bruin, Wändi

2005-03-01

Whenever competing options are considered in sequence, their evaluations may be affected by order of appearance. Such serial position effects would threaten the fairness of competitions using jury evaluations. Randomization cannot reduce potential order effects, but it does give candidates an equal chance of being assigned to preferred serial positions. Whether, or what, serial position effects emerge may depend on the cognitive demands of the judgment task. In end-of-sequence procedures, final scores are not given until all candidates have performed, possibly burdening judges' memory. If judges' evaluations are based on how well they remember performances, serial position effects may resemble those found with free recall. Candidates may also be evaluated step-by-step, immediately after each performance. This procedure should not burden memory, though it may produce different serial position effects. Yet, this paper reports similar serial position effects with end-of-sequence and step-by-step procedures used for the Eurovision Song Contest: Ratings increased with serial position. The linear order effect was replicated in the step-by-step judgments of World and European Figure Skating Contests. It is proposed that, independent of the evaluation procedure, judges' initial impressions of sequentially appearing candidates may be formed step-by-step, yielding serial position effects.

Descriptive Norms and Expectancies as Mediators of a Brief Motivational Intervention for Mandated College Students Receiving Stepped Care for Alcohol Use

PubMed Central

Yurasek, Ali M.; Borsari, Brian; Magill, Molly; Mastroleo, Nadine R.; Hustad, John T.P.; Tevyaw, Tracy O'Leary; Barnett, Nancy P.; Kahler, Christopher W.; Monti, Peter M.

2015-01-01

Background and Aims Stepped care approaches for mandated college students provide individual Brief Motivational Interventions (BMI) only for individuals who do not respond to an initial, low-intensity level of treatment such as Brief Advice (BA). However, how BMIs facilitate change in this higher-risk group of mandated students remains unclear. Perceived descriptive norms and alcohol-related expectancies are the most commonly examined mediators of BMI efficacy, but have yet to be examined in the context of stepped care. Methods Participants were mandated college students (N = 598) participating in a stepped care trial in which mandated students first received BA. Those who reported continued risky drinking 6 weeks following a BA session were randomized to either a single-session BMI (N=163) or an Assessment-only comparison condition (AO; N = 165). BMI participants reduced alcohol-related problems at the 9 month follow up significantly more than AO participants. Multiple mediation analyses using bootstrapping techniques examined whether perceived descriptive norms and alcohol-related expectancies mediated the observed outcomes. Results Reductions in perceptions of average student drinking (B = -.24; CI = -.61 to -.04) and negative expectancies (B = -.13; CI = -.38 to -.01) mediated the BMI effects. Furthermore, perceived average student norms were reduced after the BMI to levels approximating those of students who had exhibited lower risk drinking following the BA session. Conclusions Findings highlight the utility of addressing perceived norms and expectancies in BMIs, especially for students who have not responded to less intensive prevention efforts. PMID:26098125

Basis Expansion Approaches for Regularized Sequential Dictionary Learning Algorithms With Enforced Sparsity for fMRI Data Analysis.

PubMed

Seghouane, Abd-Krim; Iqbal, Asif

2017-09-01

Sequential dictionary learning algorithms have been successfully applied to functional magnetic resonance imaging (fMRI) data analysis. fMRI data sets are, however, structured data matrices with the notions of temporal smoothness in the column direction. This prior information, which can be converted into a constraint of smoothness on the learned dictionary atoms, has seldomly been included in classical dictionary learning algorithms when applied to fMRI data analysis. In this paper, we tackle this problem by proposing two new sequential dictionary learning algorithms dedicated to fMRI data analysis by accounting for this prior information. These algorithms differ from the existing ones in their dictionary update stage. The steps of this stage are derived as a variant of the power method for computing the SVD. The proposed algorithms generate regularized dictionary atoms via the solution of a left regularized rank-one matrix approximation problem where temporal smoothness is enforced via regularization through basis expansion and sparse basis expansion in the dictionary update stage. Applications on synthetic data experiments and real fMRI data sets illustrating the performance of the proposed algorithms are provided.

Measurement of the bystander intervention model for bullying and sexual harassment.

PubMed

Nickerson, Amanda B; Aloe, Ariel M; Livingston, Jennifer A; Feeley, Thomas Hugh

2014-06-01

Although peer bystanders can exacerbate or prevent bullying and sexual harassment, research has been hindered by the absence of a validated assessment tool to measure the process and sequential steps of the bystander intervention model. A measure was developed based on the five steps of Latané and Darley's (1970) bystander intervention model applied to bullying and sexual harassment. Confirmatory factor analysis with a sample of 562 secondary school students confirmed the five-factor structure of the measure. Structural equation modeling revealed that all the steps were influenced by the previous step in the model, as the theory proposed. In addition, the bystander intervention measure was positively correlated with empathy, attitudes toward bullying and sexual harassment, and awareness of bullying and sexual harassment facts. This measure can be used for future research and to inform intervention efforts related to the process of bystander intervention for bullying and sexual harassment. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Two-Step Amyloid Aggregation: Sequential Lag Phase Intermediates

NASA Astrophysics Data System (ADS)

Castello, Fabio; Paredes, Jose M.; Ruedas-Rama, Maria J.; Martin, Miguel; Roldan, Mar; Casares, Salvador; Orte, Angel

2017-01-01

The self-assembly of proteins into fibrillar structures called amyloid fibrils underlies the onset and symptoms of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. However, the molecular basis and mechanism of amyloid aggregation are not completely understood. For many amyloidogenic proteins, certain oligomeric intermediates that form in the early aggregation phase appear to be the principal cause of cellular toxicity. Recent computational studies have suggested the importance of nonspecific interactions for the initiation of the oligomerization process prior to the structural conversion steps and template seeding, particularly at low protein concentrations. Here, using advanced single-molecule fluorescence spectroscopy and imaging of a model SH3 domain, we obtained direct evidence that nonspecific aggregates are required in a two-step nucleation mechanism of amyloid aggregation. We identified three different oligomeric types according to their sizes and compactness and performed a full mechanistic study that revealed a mandatory rate-limiting conformational conversion step. We also identified the most cytotoxic species, which may be possible targets for inhibiting and preventing amyloid aggregation.

TG study of the Li0.4Fe2.4Zn0.2O4 ferrite synthesis

NASA Astrophysics Data System (ADS)

Lysenko, E. N.; Nikolaev, E. V.; Surzhikov, A. P.

2016-02-01

In this paper, the kinetic analysis of Li-Zn ferrite synthesis was studied using thermogravimetry (TG) method through the simultaneous application of non-linear regression to several measurements run at different heating rates (multivariate non-linear regression). Using TG-curves obtained for the four heating rates and Netzsch Thermokinetics software package, the kinetic models with minimal adjustable parameters were selected to quantitatively describe the reaction of Li-Zn ferrite synthesis. It was shown that the experimental TG-curves clearly suggest a two-step process for the ferrite synthesis and therefore a model-fitting kinetic analysis based on multivariate non-linear regressions was conducted. The complex reaction was described by a two-step reaction scheme consisting of sequential reaction steps. It is established that the best results were obtained using the Yander three-dimensional diffusion model at the first stage and Ginstling-Bronstein model at the second step. The kinetic parameters for lithium-zinc ferrite synthesis reaction were found and discussed.

Assembly of New Heterocycles through an Effective Use of Bisaldehydes by Using a Sequential GBB/Ugi Reaction.

PubMed

Kaur, Tanpreet; Gautam, Ram Nayan; Sharma, Anuj

2016-10-20

A facile route for the assembly of new bis-heterocyclic imidazo[2,1-b][1,3]thiazinyl/benzothiazoyl-phenyl)benzamide scaffolds through a two-step Groebke-Blackburn-Bienaymé (GBB)/Ugi reaction sequence is reported, which establishes multiple points of diversity in the final products. The highlights of this procedure are the survival of the aldehyde group following the GBB reaction without the need for additional protection/deprotection steps. Moreover, the reaction is operationally simple, with the absence of any catalyst, and exhibits excellent functional-group tolerance under minutes of microwave irradiation. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diversity-Oriented Synthesis of Coumarin-Linked Benzimidazoles via a One-Pot, Three-Step, Intramolecular Knoevenagel Cyclization.

PubMed

Yao, Po-Hsin Eric; Kumar, Sunil; Liu, Yu-Li; Fang, Chiu-Ping; Liu, Chia-Chen; Sun, Chung-Ming

2017-04-10

Diversity-oriented synthesis of coumarin-linked benzimidazoles from N-(2-aminophenyl)-2-cyanoacetamide was achieved via a one-pot, three-step sequential reaction in excellent yields. In situ intramolecular cyclization of the cyanoacetamide afforded benzimidazoles which subsequently underwent a Knoevenagel condensation of the 2-cyanomethylbenzimidazoles with salicylaldehydes promoted by triethylamine to reach the target compounds. An important intermediate, 2-(2-imino-2H-chromen-3-yl)-1H-benzimidazole was characterized by X-ray analysis and further hydrolyzed to 2-(coumarin-3-yl)benzimidazole in acidic condition. Among the synthesized compounds, some were found to be promising inhibitors of porcine kidney d-amino acid oxidase (pkDAO).

Plutonium dissolution process

DOEpatents

Vest, M.A.; Fink, S.D.; Karraker, D.G.; Moore, E.N.; Holcomb, H.P.

1994-01-01

A two-step process for dissolving Pu metal is disclosed in which two steps can be carried out sequentially or simultaneously. Pu metal is exposed to a first mixture of 1.0-1.67 M sulfamic acid and 0.0025-0.1 M fluoride, the mixture having been heated to 45-70 C. The mixture will dissolve a first portion of the Pu metal but leave a portion of the Pu in an oxide residue. Then, a mineral acid and additional fluoride are added to dissolve the residue. Alternatively, nitric acid between 0.05 and 0.067 M is added to the first mixture to dissolve the residue as it is produced. Hydrogen released during the dissolution is diluted with nitrogen.

Ruthenium-Catalyzed Cascade C—H Functionalization of Phenylacetophenones**

PubMed Central

Mehta, Vaibhav P; García-López, José-Antonio; Greaney, Michael F

2014-01-01

Three orthogonal cascade C—H functionalization processes are described, based on ruthenium-catalyzed C—H alkenylation. 1-Indanones, indeno indenes, and indeno furanones were accessed through cascade pathways by using arylacetophenones as substrates under conditions of catalytic [{Ru(p-cymene)Cl2}2] and stoichiometric Cu(OAc)2. Each transformation uses C—H functionalization methods to form C—C bonds sequentially, with the indeno furanone synthesis featuring a C—O bond formation as the terminating step. This work demonstrates the power of ruthenium-catalyzed alkenylation as a platform reaction to develop more complex transformations, with multiple C—H functionalization steps taking place in a single operation to access novel carbocyclic structures. PMID:24453063

Device for rapid quantification of human carotid baroreceptor-cardiac reflex responses

NASA Technical Reports Server (NTRS)

Sprenkle, J. M.; Eckberg, D. L.; Goble, R. L.; Schelhorn, J. J.; Halliday, H. C.

1986-01-01

A new device has been designed, constructed, and evaluated to characterize the human carotid baroreceptor-cardiac reflex response relation rapidly. This system was designed for study of reflex responses of astronauts before, during, and after space travel. The system comprises a new tightly sealing silicon rubber neck chamber, a stepping motor-driven electrodeposited nickel bellows pressure system, capable of delivering sequential R-wave-triggered neck chamber pressure changes between +40 and -65 mmHg, and a microprocessor-based electronics system for control of pressure steps and analysis and display of responses. This new system provokes classic sigmoid baroreceptor-cardiac reflex responses with threshold, linear, and saturation ranges in most human volunteers during one held expiration.

Enhanced Performance of Perovskite CH3NH3PbI3 Solar Cell by Using CH3NH3I as Additive in Sequential Deposition.

PubMed

Xie, Yian; Shao, Feng; Wang, Yaoming; Xu, Tao; Wang, Deliang; Huang, Fuqiang

2015-06-17

Sequential deposition is a widely adopted method to prepare CH3NH3PbI3 on mesostructured TiO2 electrode for organic lead halide perovskite solar cells. However, this method often suffers from the uncontrollable crystal size, surface morphology, and residual PbI2 in the resulting CH3NH3PbI3, which are all detrimental to the device performance. We herein present an optimized sequential solution deposition method by introducing different amount of CH3NH3I in PbI2 precursor solution in the first step to prepare CH3NH3PbI3 absorber on mesoporous TiO2 substrates. The addition of CH3NH3I in PbI2 precursor solution can affect the crystallization and composition of PbI2 raw films, resulting in the variation of UV-vis absorption and surface morphology. Proper addition of CH3NH3I not only enhances the absorption but also improves the efficiency of CH3NH3PbI3 solar cells from 11.13% to 13.37%. Photoluminescence spectra suggest that the improvement of device performance is attributed to the decrease of recombination rate of carriers in CH3NH3PbI3 absorber. This current method provides a highly repeatable route for enhancing the efficiency of CH3NH3PbI3 solar cell in the sequential solution deposition method.

The Biological Effects of Quadripolar Radiofrequency Sequential Application: A Human Experimental Study

PubMed Central

Cornaglia, Antonia Icaro; Faga, Angela; Scevola, Silvia

2014-01-01

Abstract Objective: An experimental study was conducted to assess the effectiveness and safety of an innovative quadripolar variable electrode configuration radiofrequency device with objective measurements in an ex vivo and in vivo human experimental model. Background data: Nonablative radiofrequency applications are well-established anti-ageing procedures for cosmetic skin tightening. Methods: The study was performed in two steps: ex vivo and in vivo assessments. In the ex vivo assessments the radiofrequency applications were performed on human full-thickness skin and subcutaneous tissue specimens harvested during surgery for body contouring. In the in vivo assessments the applications were performed on two volunteer patients scheduled for body contouring surgery at the end of the study. The assessment methods were: clinical examination and medical photography, temperature measurement with thermal imaging scan, and light microscopy histological examination. Results: The ex vivo assessments allowed for identification of the effective safety range for human application. The in vivo assessments allowed for demonstration of the biological effects of sequential radiofrequency applications. After a course of radiofrequency applications, the collagen fibers underwent an immediate heat-induced rearrangement and were partially denaturated and progressively metabolized by the macrophages. An overall thickening and spatial rearrangement was appreciated both in the collagen and elastic fibers, the latter displaying a juvenile reticular pattern. A late onset in the macrophage activation after sequential radiofrequency applications was appreciated. Conclusions: Our data confirm the effectiveness of sequential radiofrequency applications in obtaining attenuation of the skin wrinkles by an overall skin tightening. PMID:25244081

Sequential Tool Use in Great Apes

PubMed Central

Martin-Ordas, Gema; Schumacher, Lena; Call, Josep

2012-01-01

Sequential tool use is defined as using a tool to obtain another non-food object which subsequently itself will serve as a tool to act upon a further (sub)goal. Previous studies have shown that birds and great apes succeed in such tasks. However, the inclusion of a training phase for each of the sequential steps and the low cost associated with retrieving the longest tools limits the scope of the conclusions. The goal of the experiments presented here was, first to replicate a previous study on sequential tool use conducted on New Caledonian crows and, second, extend this work by increasing the cost of retrieving a tool in order to test tool selectivity of apes. In Experiment 1, we presented chimpanzees, orangutans and bonobos with an out-of-reach reward, two tools that were available but too short to reach the food and four out-of-reach tools differing in functionality. Similar to crows, apes spontaneously used up to 3 tools in sequence to get the reward and also showed a strong preference for the longest out-of reach tool independently of the distance of the food. In Experiment 2, we increased the cost of reaching for the longest out-of reach tool. Now apes used up to 5 tools in sequence to get the reward and became more selective in their choice of the longest tool as the costs of its retrieval increased. The findings of the studies presented here contribute to the growing body of comparative research on tool use. PMID:23300592

The biological effects of quadripolar radiofrequency sequential application: a human experimental study.

PubMed

Nicoletti, Giovanni; Cornaglia, Antonia Icaro; Faga, Angela; Scevola, Silvia

2014-10-01

An experimental study was conducted to assess the effectiveness and safety of an innovative quadripolar variable electrode configuration radiofrequency device with objective measurements in an ex vivo and in vivo human experimental model. Nonablative radiofrequency applications are well-established anti-ageing procedures for cosmetic skin tightening. The study was performed in two steps: ex vivo and in vivo assessments. In the ex vivo assessments the radiofrequency applications were performed on human full-thickness skin and subcutaneous tissue specimens harvested during surgery for body contouring. In the in vivo assessments the applications were performed on two volunteer patients scheduled for body contouring surgery at the end of the study. The assessment methods were: clinical examination and medical photography, temperature measurement with thermal imaging scan, and light microscopy histological examination. The ex vivo assessments allowed for identification of the effective safety range for human application. The in vivo assessments allowed for demonstration of the biological effects of sequential radiofrequency applications. After a course of radiofrequency applications, the collagen fibers underwent an immediate heat-induced rearrangement and were partially denaturated and progressively metabolized by the macrophages. An overall thickening and spatial rearrangement was appreciated both in the collagen and elastic fibers, the latter displaying a juvenile reticular pattern. A late onset in the macrophage activation after sequential radiofrequency applications was appreciated. Our data confirm the effectiveness of sequential radiofrequency applications in obtaining attenuation of the skin wrinkles by an overall skin tightening.

Protein-protein interactions and metabolite channelling in the plant tricarboxylic acid cycle

PubMed Central

Zhang, Youjun; Beard, Katherine F. M.; Swart, Corné; Bergmann, Susan; Krahnert, Ina; Nikoloski, Zoran; Graf, Alexander; Ratcliffe, R. George; Sweetlove, Lee J.; Fernie, Alisdair R.; Obata, Toshihiro

2017-01-01

Protein complexes of sequential metabolic enzymes, often termed metabolons, may permit direct channelling of metabolites between the enzymes, providing increased control over metabolic pathway fluxes. Experimental evidence supporting their existence in vivo remains fragmentary. In the present study, we test binary interactions of the proteins constituting the plant tricarboxylic acid (TCA) cycle. We integrate (semi-)quantitative results from affinity purification-mass spectrometry, split-luciferase and yeast-two-hybrid assays to generate a single reliability score for assessing protein–protein interactions. By this approach, we identify 158 interactions including those between catalytic subunits of sequential enzymes and between subunits of enzymes mediating non-adjacent reactions. We reveal channelling of citrate and fumarate in isolated potato mitochondria by isotope dilution experiments. These results provide evidence for a functional TCA cycle metabolon in plants, which we discuss in the context of contemporary understanding of this pathway in other kingdoms. PMID:28508886

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

PubMed Central

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-01-01

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. PMID:26240385

Emotional neglect in childhood shapes social dysfunctioning in adults by influencing the oxytocin and the attachment system: Results from a population-based study.

PubMed

Müller, Laura E; Bertsch, Katja; Bülau, Konstatin; Herpertz, Sabine C; Buchheim, Anna

2018-06-01

Early life maltreatment (ELM) is the major single risk factor for impairments in social functioning and mental health in adulthood. One of the most prevalent and most rapidly increasing forms of ELM is emotional neglect. According to bio-behavioral synchrony assumptions, the oxytocin and attachment systems play an important mediating role in the interplay between emotional neglect and social dysfunctioning. Therefore, the aim of the present study was to investigate whether fear and avoidance of social functioning, two important and highly prevalent facets of social dysfunctioning in adulthood, are shaped by emotional neglect, plasma oxytocin levels and attachment representations. We assessed emotional neglect as well as other forms of ELM with the Childhood Trauma Questionnaire, current attachment representations with the Adult Attachment Projective Picture System, and fear and avoidance of social situations with the Liebowitz Social Anxiety Scale in a population-based sample of N = 121 men and women. Furthermore, 4.9 ml blood samples were drawn from each participant to assess peripheral plasma oxytocin levels. Applying a sequential mediation model, results revealed that emotional neglect was associated with lower plasma oxytocin levels which in turn were associated with insecure attachment representations which were related to elevated fear and avoidance of social situations (a 1 d 21 b 2 : F 3,117  = 20.84, P < .001). Plasma oxytocin and current attachment representations hence fully and sequentially mediate the effects of emotional neglect on social fear and avoidance, two important facets of adult social dysfunctioning, confirming bio-behavioral synchrony assumptions. Copyright © 2018. Published by Elsevier B.V.

Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence: A Putative Mechanistic Neurodevelopmental Pathway.

PubMed

Luby, Joan L; Barch, Deanna; Whalen, Diana; Tillman, Rebecca; Belden, Andy

2017-12-01

Adverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood. To investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes. A prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit. Early life adversity. Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years. The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively. Study findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.

The sequential use of washing and an electrochemical reduction process for the remediation of lead-contaminated soils.

PubMed

Demir, Aydeniz; Köleli, Nurcan

2013-01-01

A two-step method for the remediation of three different types of lead (Pb)-contaminated soil was evaluated. The first step included soil washing with ethylenediaminetetraacetic acid (EDTA) to remove Pb from soils. The washing experiments were performed with 0.05 M Na2EDTA at 1:10 soil to liquid ratio. Following the washing, Pb removal efficiency from soils ranged within 50-70%. After the soil washing process, Pb2+ ions in the washing solution were reduced electrochemically in a fixed-bed reactor. Lead removal efficiency with the electrochemical reduction at -2.0 V potential ranged within 57-76%. The overall results indicate that this two-step method is an environmentally-friendly and effective technology to remediate Pb-contaminated soils, as well as Pb-contaminated wastewater treatment due to the transformation of toxic Pb2+ ions into a non-hazardous metallic form (Pb(0)).

Neural networks for vertical microcode compaction

NASA Astrophysics Data System (ADS)

Chu, Pong P.

1992-09-01

Neural networks provide an alternative way to solve complex optimization problems. Instead of performing a program of instructions sequentially as in a traditional computer, neural network model explores many competing hypotheses simultaneously using its massively parallel net. The paper shows how to use the neural network approach to perform vertical micro-code compaction for a micro-programmed control unit. The compaction procedure includes two basic steps. The first step determines the compatibility classes and the second step selects a minimal subset to cover the control signals. Since the selection process is an NP- complete problem, to find an optimal solution is impractical. In this study, we employ a customized neural network to obtain the minimal subset. We first formalize this problem, and then define an `energy function' and map it to a two-layer fully connected neural network. The modified network has two types of neurons and can always obtain a valid solution.

Process for conversion of lignin to reformulated hydrocarbon gasoline

DOEpatents

Shabtai, Joseph S.; Zmierczak, Wlodzimierz W.; Chornet, Esteban

1999-09-28

A process for converting lignin into high-quality reformulated hydrocarbon gasoline compositions in high yields is disclosed. The process is a two-stage, catalytic reaction process that produces a reformulated hydrocarbon gasoline product with a controlled amount of aromatics. In the first stage, a lignin material is subjected to a base-catalyzed depolymerization reaction in the presence of a supercritical alcohol as a reaction medium, to thereby produce a depolymerized lignin product. In the second stage, the depolymerized lignin product is subjected to a sequential two-step hydroprocessing reaction to produce a reformulated hydrocarbon gasoline product. In the first hydroprocessing step, the depolymerized lignin is contacted with a hydrodeoxygenation catalyst to produce a hydrodeoxygenated intermediate product. In the second hydroprocessing step, the hydrodeoxygenated intermediate product is contacted with a hydrocracking/ring hydrogenation catalyst to produce the reformulated hydrocarbon gasoline product which includes various desirable naphthenic and paraffinic compounds.

Facially Selective Cu-catalyzed Carbozincation of Cyclopropenes Using Arylzinc Reagents Formed by Sequential I/Mg/Zn exchange

PubMed Central

Tarwade, Vinod; Selvaraj, Ramajeyam; Fox, Joseph M.

2012-01-01

Described is a Cu-catalyzed directed carbozincation of cyclopropenes with organozinc reagents prepared by I/Mg/Zn exchange. This protocol broadens the scope with respect to functional group tolerance and enables use of aryl iodide precursors, rather than purified diorganozinc precursors. Critical to diastereoselectivity of the carbozincation step is the removal of magnesium halide salts after transmetallation with ZnCl2. PMID:23035947

F-16 Training System Media Report

DTIC Science & Technology

1981-03-01

practice items. 4.1.3 Use/Procedure This strategy requires the learner to apply a set of sequential steps designed to accomplish a specific task which needs...information. 6. Feedback: Provides the student with the correct answers for the practice items. 4.1.5 Use/Rule This strategy requires the learner to...provide the background and rationale for selecting and/or modifying instructional media to best meet the needs of the F-16 training program. The

Sequential allylic substitution/Pauson-Khand reaction: a strategy to bicyclic fused cyclopentenones from MBH-acetates of acetylenic aldehydes.

PubMed

Raji Reddy, Chada; Kumaraswamy, Paridala; Singarapu, Kiran K

2014-09-05

An efficient approach for the construction of novel bicyclic fused cyclopentenones starting from Morita-Baylis-Hillman (MBH) acetates of acetylenic aldehydes with flexible scaffold diversity has been achieved using a two-step reaction sequence involving allylic substitution and the Pauson-Khand reaction. This strategy provided a facile access to various bicyclic cyclopentenones fused with either a carbocyclic or a heterocyclic ring system in good yield.

Separation and preconcentration of the rare-earth elements and yttrium from geological materials by ion-exchange and sequential acid elution

USGS Publications Warehouse

Crock, J.G.; Lichte, F.E.; Riddle, G.O.; Beech, C.L.

1986-01-01

The abundance of rare-earth elements (REE) and yttrium in geological materials is generally low, and most samples contain elements that interfere in the determination of the REE and Y, so a separation and/or preconcentration step is often necessary. This is often achieved by ion-exchange chromatography with either nitric or hydrochloric acid. It is advantageous, however, to use both acids sequentially. The final solution thus obtained contains only the REE and Y, with minor amounts of Al, Ba, Ca, Sc, Sr and Ti. Elements that potentially interfere, such as Be, Co, Cr, Fe, Mn, Th, U, V and Zr, are virtually eliminated. Inductively-coupled argon plasma atomic-emission spectroscopy can then be used for a final precise and accurate measurement. The method can also be used with other instrumental methods of analysis. ?? 1986.

Amyloid Precursor Protein Processing and Alzheimer’s Disease

PubMed Central

O’Brien, Richard J.; Wong, Philip C.

2011-01-01

Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (APP) proteolysis is the crucial step in the development of AD. APP is a single-pass transmembrane protein expressed at high levels in the brain and metabolized in a rapid and highly complex fashion by a series of sequential proteases, including the intramembranous γ-secretase complex, which also process other key regulatory molecules. Why Aβ accumulates in the brains of elderly individuals is unclear but could relate to changes in APP metabolism or Aβ elimination. Lessons learned from biochemical and genetic studies of APP processing will be crucial to the development of therapeutic targets to treat AD. PMID:21456963

Fine-Tuning the Antimicrobial Profile of Biocompatible Gold Nanoparticles by Sequential Surface Functionalization Using Polyoxometalates and Lysine

PubMed Central

Daima, Hemant K.; Selvakannan, P. R.; Shukla, Ravi; Bhargava, Suresh K.; Bansal, Vipul

2013-01-01

Antimicrobial action of nanomaterials is typically assigned to the nanomaterial composition, size and/or shape, whereas influence of complex corona stabilizing the nanoparticle surface is often neglected. We demonstrate sequential surface functionalization of tyrosine-reduced gold nanoparticles (AuNPsTyr) with polyoxometalates (POMs) and lysine to explore controlled chemical functionality-driven antimicrobial activity. Our investigations reveal that highly biocompatible gold nanoparticles can be tuned to be a strong antibacterial agent by fine-tuning their surface properties in a controllable manner. The observation from the antimicrobial studies on a gram negative bacterium Escherichia coli were further validated by investigating the anticancer properties of these step-wise surface-controlled materials against A549 human lung carcinoma cells, which showed a similar toxicity pattern. These studies highlight that the nanomaterial toxicity and biological applicability are strongly governed by their surface corona. PMID:24147146

Fine-tuning the antimicrobial profile of biocompatible gold nanoparticles by sequential surface functionalization using polyoxometalates and lysine.

PubMed

Daima, Hemant K; Selvakannan, P R; Shukla, Ravi; Bhargava, Suresh K; Bansal, Vipul

2013-01-01

Antimicrobial action of nanomaterials is typically assigned to the nanomaterial composition, size and/or shape, whereas influence of complex corona stabilizing the nanoparticle surface is often neglected. We demonstrate sequential surface functionalization of tyrosine-reduced gold nanoparticles (AuNPs(Tyr)) with polyoxometalates (POMs) and lysine to explore controlled chemical functionality-driven antimicrobial activity. Our investigations reveal that highly biocompatible gold nanoparticles can be tuned to be a strong antibacterial agent by fine-tuning their surface properties in a controllable manner. The observation from the antimicrobial studies on a gram negative bacterium Escherichia coli were further validated by investigating the anticancer properties of these step-wise surface-controlled materials against A549 human lung carcinoma cells, which showed a similar toxicity pattern. These studies highlight that the nanomaterial toxicity and biological applicability are strongly governed by their surface corona.

Cooperative working of bacterial chromosome replication proteins generated by a reconstituted protein expression system

PubMed Central

Fujiwara, Kei; Katayama, Tsutomu; Nomura, Shin-ichiro M.

2013-01-01

Replication of all living cells relies on the multirounds flow of the central dogma. Especially, expression of DNA replication proteins is a key step to circulate the processes of the central dogma. Here we achieved the entire sequential transcription–translation–replication process by autonomous expression of chromosomal DNA replication machineries from a reconstituted transcription–translation system (PURE system). We found that low temperature is essential to express a complex protein, DNA polymerase III, in a single tube using the PURE system. Addition of the 13 genes, encoding initiator, DNA helicase, helicase loader, RNA primase and DNA polymerase III to the PURE system gave rise to a DNA replication system by a coupling manner. An artificial genetic circuit demonstrated that the DNA produced as a result of the replication is able to provide genetic information for proteins, indicating the in vitro central dogma can sequentially undergo two rounds. PMID:23737447

Operation of a single-channel, sequential Navstar GPS receiver in a helicopter mission environment

NASA Technical Reports Server (NTRS)

Edwards, F. G.; Hamlin, J. R.

1984-01-01

It is pointed out that the future utilization of the Navstar Global Positioning System (GPS) by civil helicopters will provide an enhanced performance not obtainable with current navigations systems. GPS will supply properly equipped users with extremely accurate three-dimensional position and velocity information anywhere in the world. Preliminary studies have been conducted to investigate differential GPS concept mechanizations and cost, and to theoretically predict navigation performance and the impact of degradation of the GPS C/A code for national security considerations. The obtained results are encouraging, but certain improvements are needed. As a second step in the program, a single-channel sequential GPS navigator was installed and operated in the NASA SH-3G helicopter. A series of flight tests were conducted. It is found that performance of the Navstar GPS Z-set is quite acceptable to support area navigation and nonprecision approach operations.

Semi-Automated Hydrophobic Interaction Chromatography Column Scouting Used in the Two-Step Purification of Recombinant Green Fluorescent Protein

PubMed Central

Murphy, Patrick J. M.

2014-01-01

Background Hydrophobic interaction chromatography (HIC) most commonly requires experimental determination (i.e., scouting) in order to select an optimal chromatographic medium for purifying a given target protein. Neither a two-step purification of untagged green fluorescent protein (GFP) from crude bacterial lysate using sequential HIC and size exclusion chromatography (SEC), nor HIC column scouting elution profiles of GFP, have been previously reported. Methods and Results Bacterial lysate expressing recombinant GFP was sequentially adsorbed to commercially available HIC columns containing butyl, octyl, and phenyl-based HIC ligands coupled to matrices of varying bead size. The lysate was fractionated using a linear ammonium phosphate salt gradient at constant pH. Collected HIC eluate fractions containing retained GFP were then pooled and further purified using high-resolution preparative SEC. Significant differences in presumptive GFP elution profiles were observed using in-line absorption spectrophotometry (A395) and post-run fluorimetry. SDS-PAGE and western blot demonstrated that fluorometric detection was the more accurate indicator of GFP elution in both HIC and SEC purification steps. Comparison of composite HIC column scouting data indicated that a phenyl ligand coupled to a 34 µm matrix produced the highest degree of target protein capture and separation. Conclusions Conducting two-step protein purification using the preferred HIC medium followed by SEC resulted in a final, concentrated product with >98% protein purity. In-line absorbance spectrophotometry was not as precise of an indicator of GFP elution as post-run fluorimetry. These findings demonstrate the importance of utilizing a combination of detection methods when evaluating purification strategies. GFP is a well-characterized model protein, used heavily in educational settings and by researchers with limited protein purification experience, and the data and strategies presented here may aid in development other of HIC-compatible protein purification schemes. PMID:25254496

Examining a Sequential Mediation Model of Chinese University Students’ Well-Being: A Career Construction Perspective

PubMed Central

Zhuang, Mingke; She, Zhuolin; Cai, Zijun; Huang, Zheng; Xiang, Qian; Wang, Ping; Zhu, Fei

2018-01-01

Despite career construction theory attends to individual subjective career and provides a useful lens to study well-being, extant research has yielded limited insights into the mechanisms through which career construction variables influence individual well-being. To address this important gap, the present study examined a mediation model that links indicators of career adaptivity (big-five personality and approach/avoidance traits) to psychological well-being (psychological flourishing and life satisfaction) through career adaptability and in sequent meaning of life (presence of life meaning and search for life meaning) among a sample of Chinese university students (N = 165). The results of a two-wave survey study showed that career adaptability and presence of life meaning mediated the effects of openness to experience, consciousness, approach trait, and avoidance trait on individual well-being in sequence. The results also showed that approach trait’s effect on presence of meaning was partially mediated by career adaptability; career adaptability’s effect on psychological flourishing was partially mediated by presence of meaning. These findings advance understanding of antecedents to individual well-being from a career construction perspective, and carry implications for career education and counseling practices. PMID:29743876

Examining a Sequential Mediation Model of Chinese University Students' Well-Being: A Career Construction Perspective.

PubMed

Zhuang, Mingke; She, Zhuolin; Cai, Zijun; Huang, Zheng; Xiang, Qian; Wang, Ping; Zhu, Fei

2018-01-01

Despite career construction theory attends to individual subjective career and provides a useful lens to study well-being, extant research has yielded limited insights into the mechanisms through which career construction variables influence individual well-being. To address this important gap, the present study examined a mediation model that links indicators of career adaptivity (big-five personality and approach/avoidance traits) to psychological well-being (psychological flourishing and life satisfaction) through career adaptability and in sequent meaning of life (presence of life meaning and search for life meaning) among a sample of Chinese university students ( N = 165). The results of a two-wave survey study showed that career adaptability and presence of life meaning mediated the effects of openness to experience, consciousness, approach trait, and avoidance trait on individual well-being in sequence. The results also showed that approach trait's effect on presence of meaning was partially mediated by career adaptability; career adaptability's effect on psychological flourishing was partially mediated by presence of meaning. These findings advance understanding of antecedents to individual well-being from a career construction perspective, and carry implications for career education and counseling practices.

How Internal Political Efficacy Translates Political Knowledge Into Political Participation

PubMed Central

Reichert, Frank

2016-01-01

This study presents evidence for the mediation effect of political knowledge through political self-efficacy (i.e. internal political efficacy) in the prediction of political participation. It employs an action theoretic approach—by and large grounded on the Theory of Planned Behaviour—and uses data from the German Longitudinal Election Study to examine whether political knowledge has distinct direct effects on voting, conventional, and/or unconventional political participation. It argues that political knowledge raises internal political efficacy and thereby indirectly increases the chance that a citizen will participate in politics. The results of mediated multiple regression analyses yield evidence that political knowledge indeed translates into internal political efficacy, thus it affects political participation of various kinds indirectly. However, internal political efficacy and intentions to participate politically yield simultaneous direct effects only on conventional political participation. Sequentially mediated effects appear for voting and conventional political participation, with political knowledge being mediated by internal political efficacy and subsequently also by behavioural intentions. The mediation patterns for unconventional political participation are less clear though. The discussion accounts for restrictions of this study and points to questions for answer by future research. PMID:27298633

Critical evaluation of the ability of sequential extraction procedures to quantify discrete forms of selenium in sediments and soils.

PubMed

Wright, Michael T; Parker, David R; Amrhein, Christopher

2003-10-15

Sequential extraction procedures (SEPs) have been widely used to characterize the mobility, bioavailibility, and potential toxicity of trace elements in soils and sediments. Although oft-criticized, these methods may perform best with redox-labile elements (As, Hg, Se) for which more discrete biogeochemical phases may arise from variations in oxidation number. We critically evaluated two published SEPs for Se for their specificity and precision by applying them to four discrete components in an inert silica matrix: soluble Se(VI) (selenate), Se(IV) (selenite) adsorbed onto goethite, elemental Se, and a metal selenide (FeSe; achavalite). These were extracted both individually and in a mixed model sediment. The more selective of the two procedures was modified to further improve its selectivity (SEP 2M). Both SEP 1 and SEP 2M quantitatively recovered soluble selenate but yielded incomplete recoveries of adsorbed selenite (64% and 81%, respectively). SEP 1 utilizes 0.1 M K2S2O8 to target "organically associated" Se, but this extractant also solubilized most of the elemental (64%) and iron selenide (91%) components of the model sediment. In SEP 2M, the Na2SO3 used in step III is effective in extracting elemental Se but also extracted 17% of the Se from the iron selenide, such that the elemental fraction would be overestimated should both forms coexist. Application of SEP 2M to eight wetland sediments further suggested that the Na2SO3 in step III extracts some organically associated Se, so a NaOH extraction was inserted beforehand to yield a further modification, SEP 2OH. Results using this five-step procedure suggested that the four-step SEP 2M could overestimate elemental Se by as much as 43% due to solubilization of organic Se. Although still imperfect in its selectivity, SEP 20H may be the most suitable procedure for routine, accurate fractionation of Se in soils and sediments. However, the strong oxidant (NaOCl) used in the final step cannot distinguish between refractory organic forms of Se and pyritic Se that might form under sulfur-reducing conditions.

Sequential replication-coupled destruction at G1/S ensures genome stability

PubMed Central

Coleman, Kate E.; Grant, Gavin D.; Haggerty, Rachel A.; Brantley, Kristen; Shibata, Etsuko; Workman, Benjamin D.; Dutta, Anindya; Varma, Dileep; Purvis, Jeremy E.; Cook, Jeanette Gowen

2015-01-01

Timely ubiquitin-mediated protein degradation is fundamental to cell cycle control, but the precise degradation order at each cell cycle phase transition is still unclear. We investigated the degradation order among substrates of a single human E3 ubiquitin ligase, CRL4Cdt2, which mediates the S-phase degradation of key cell cycle proteins, including Cdt1, PR-Set7, and p21. Our analysis of synchronized cells and asynchronously proliferating live single cells revealed a consistent order of replication-coupled destruction during both S-phase entry and DNA repair; Cdt1 is destroyed first, whereas p21 destruction is always substantially later than that of Cdt1. These differences are attributable to the CRL4Cdt2 targeting motif known as the PIP degron, which binds DNA-loaded proliferating cell nuclear antigen (PCNADNA) and recruits CRL4Cdt2. Fusing Cdt1's PIP degron to p21 causes p21 to be destroyed nearly concurrently with Cdt1 rather than consecutively. This accelerated degradation conferred by the Cdt1 PIP degron is accompanied by more effective Cdt2 recruitment by Cdt1 even though p21 has higher affinity for PCNADNA. Importantly, cells with artificially accelerated p21 degradation display evidence of stalled replication in mid-S phase and sensitivity to replication arrest. We therefore propose that sequential degradation ensures orderly S-phase progression to avoid replication stress and genome instability. PMID:26272819

CRISPR/Cas9 mediated sequential editing of genes critical for ookinete motility in Plasmodium yoelii.

PubMed

Zhang, Cui; Gao, Han; Yang, Zhenke; Jiang, Yuanyuan; Li, Zhenkui; Wang, Xu; Xiao, Bo; Su, Xin-Zhuan; Cui, Huiting; Yuan, Jing

2017-03-01

CRISPR/Cas9 has been successfully adapted for gene editing in malaria parasites including Plasmodium falciparum and Plasmodium yoelii. However, the reported methods were limited to editing one gene at a time. In practice, it is often desired to modify multiple genetic loci in a parasite genome. Here we describe a CRISPR/Cas9 mediated genome editing method that allows successive modification of more than one gene in the genome of P. yoelii using an improved single-vector system (pYCm) we developed previously. Drug resistant genes encoding human dihydrofolate reductase (hDHFR) and a yeast bifunctional protein (yFCU), with cytosine deaminase (CD) and uridyl phosphoribosyl transferase (UPRT) activities in the plasmid, allowed sequential positive (pyrimethamine, Pyr) and negative (5-fluorocytosine, 5FC) selections and generation of transgenic parasites free of the episomal plasmid after genetic modification. Using this system, we were able to efficiently tag a gene of interest (Pyp28) and subsequently disrupted two genes (Pyctrp and Pycdpk3) that are individually critical for ookinete motility. Disruption of the genes either eliminated (Pyctrp) or greatly reduced (Pycdpk3) ookinete forward motility in matrigel in vitro and completely blocked oocyst development in mosquito midgut. The method will greatly facilitate studies of parasite gene function, development, and disease pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Prototype Willingness Model Drinking Cognitions Mediate Personalized Normative Feedback Efficacy.

PubMed

Lewis, Melissa A; Litt, Dana M; Tomkins, Mary; Neighbors, Clayton

2017-05-01

Personalized normative feedback (PNF) interventions have been shown to be efficacious at reducing college student drinking. Because descriptive norms have been shown to mediate PNF efficacy, the current study focused on examining additional prototype willingness model social reaction cognitions, namely, prototypes and willingness, as mediators of intervention efficacy. We expected the PNF interventions to be associated with increased prototype favorability of students who do not drink, which would in turn be associated with decreased willingness to drink and subsequently, less drinking. The current study included 622 college students (53.2% women; 62% Caucasian) who reported one or more heavy drinking episodes in the past month and completed baseline and three-month follow-up assessments. As posited by the framework of the prototype willingness model, sequential mediation analyses were conducted to evaluate increases in abstainer prototype favorability on willingness on drinking, and subsequently willingness to drink on drinking behavior. Mediation results revealed significant indirect effects of PNF on three-month drinking through three-month prototypes and willingness, indicating that the social reaction pathway of the prototype willingness model was supported. Findings have important implications for PNF interventions aiming to reduce high-risk drinking among college students. Study findings suggest that we should consider looking at additional socially-based mediators of PNF efficacy in addition to perceived descriptive norms.

Prototype Willingness Model Drinking Cognitions Mediate Personalized Normative Feedback Efficacy

PubMed Central

Litt, Dana M.; Tomkins, Mary; Neighbors, Clayton

2017-01-01

Personalized normative feedback (PNF) interventions have been shown to be efficacious at reducing college student drinking. Because descriptive norms have been shown to mediate PNF efficacy, the current study focused on examining additional prototype willingness model social reaction cognitions, namely, prototypes and willingness, as mediators of intervention efficacy. We expected the PNF interventions to be associated with increased prototype favorability of students who do not drink, which would in turn be associated with decreased willingness to drink and subsequently, less drinking. The current study included 622 college students (53.2% women; 62% Caucasian) who reported one or more heavy drinking episodes in the past month and completed baseline and three-month follow-up assessments. As posited by the framework of the prototype willingness model, sequential mediation analyses were conducted to evaluate increases in abstainer prototype favorability on willingness on drinking, and subsequently willingness to drink on drinking behavior. Mediation results revealed significant indirect effects of PNF on three-month drinking through three-month prototypes and willingness, indicating that the social reaction pathway of the prototype willingness model was supported. Findings have important implications for PNF interventions aiming to reduce high-risk drinking among college students. Study findings suggest that we should consider looking at additional socially-based mediators of PNF efficacy in addition to perceived descriptive norms. PMID:27995431

Sequential sampling of visual objects during sustained attention.

PubMed

Jia, Jianrong; Liu, Ling; Fang, Fang; Luo, Huan

2017-06-01

In a crowded visual scene, attention must be distributed efficiently and flexibly over time and space to accommodate different contexts. It is well established that selective attention enhances the corresponding neural responses, presumably implying that attention would persistently dwell on the task-relevant item. Meanwhile, recent studies, mostly in divided attentional contexts, suggest that attention does not remain stationary but samples objects alternately over time, suggesting a rhythmic view of attention. However, it remains unknown whether the dynamic mechanism essentially mediates attentional processes at a general level. Importantly, there is also a complete lack of direct neural evidence reflecting whether and how the brain rhythmically samples multiple visual objects during stimulus processing. To address these issues, in this study, we employed electroencephalography (EEG) and a temporal response function (TRF) approach, which can dissociate responses that exclusively represent a single object from the overall neuronal activity, to examine the spatiotemporal characteristics of attention in various attentional contexts. First, attention, which is characterized by inhibitory alpha-band (approximately 10 Hz) activity in TRFs, switches between attended and unattended objects every approximately 200 ms, suggesting a sequential sampling even when attention is required to mostly stay on the attended object. Second, the attentional spatiotemporal pattern is modulated by the task context, such that alpha-mediated switching becomes increasingly prominent as the task requires a more uniform distribution of attention. Finally, the switching pattern correlates with attentional behavioral performance. Our work provides direct neural evidence supporting a generally central role of temporal organization mechanism in attention, such that multiple objects are sequentially sorted according to their priority in attentional contexts. The results suggest that selective attention, in addition to the classically posited attentional "focus," involves a dynamic mechanism for monitoring all objects outside of the focus. Our findings also suggest that attention implements a space (object)-to-time transformation by acting as a series of concatenating attentional chunks that operate on 1 object at a time.

Sequential sampling of visual objects during sustained attention

PubMed Central

Jia, Jianrong; Liu, Ling; Fang, Fang

2017-01-01

In a crowded visual scene, attention must be distributed efficiently and flexibly over time and space to accommodate different contexts. It is well established that selective attention enhances the corresponding neural responses, presumably implying that attention would persistently dwell on the task-relevant item. Meanwhile, recent studies, mostly in divided attentional contexts, suggest that attention does not remain stationary but samples objects alternately over time, suggesting a rhythmic view of attention. However, it remains unknown whether the dynamic mechanism essentially mediates attentional processes at a general level. Importantly, there is also a complete lack of direct neural evidence reflecting whether and how the brain rhythmically samples multiple visual objects during stimulus processing. To address these issues, in this study, we employed electroencephalography (EEG) and a temporal response function (TRF) approach, which can dissociate responses that exclusively represent a single object from the overall neuronal activity, to examine the spatiotemporal characteristics of attention in various attentional contexts. First, attention, which is characterized by inhibitory alpha-band (approximately 10 Hz) activity in TRFs, switches between attended and unattended objects every approximately 200 ms, suggesting a sequential sampling even when attention is required to mostly stay on the attended object. Second, the attentional spatiotemporal pattern is modulated by the task context, such that alpha-mediated switching becomes increasingly prominent as the task requires a more uniform distribution of attention. Finally, the switching pattern correlates with attentional behavioral performance. Our work provides direct neural evidence supporting a generally central role of temporal organization mechanism in attention, such that multiple objects are sequentially sorted according to their priority in attentional contexts. The results suggest that selective attention, in addition to the classically posited attentional “focus,” involves a dynamic mechanism for monitoring all objects outside of the focus. Our findings also suggest that attention implements a space (object)-to-time transformation by acting as a series of concatenating attentional chunks that operate on 1 object at a time. PMID:28658261

Functional analysis of the interactions between reovirus particles and various proteases in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sargent, M.D.; Long, D.G.; Borsa, J.

1977-01-01

The digestion of purified reovirus particles by various proteases including chymotrypsin, trypsin, pronase, papain, bromelain, proteinase K, and fibrinolysin has been examined as it relates to virion transcriptase activation and alteration of infectivity. In every case uncoating to the level of active transcriptase proceeds via two mechanistically distinct steps. All the proteases tested serve to mediate only the first of the two steps, converting intact virions to intermediate subviral particles (ISVP) in which the transcriptase is retained in a latent state. The second step of the uncoating process is mediated by a K/sup +/ ion-triggered, endogenous mechanism and results inmore » conversion of ISVP to cores, concomitant with transcriptase activation and loss of infectivity. All of the tested enzymes, except trypsin, reversibly block the second step of uncoating. These results indicate the generality, with respect to protease employed, of the two-step process for reovirus uncoating and transcriptase activation demonstrated previously with chymotrypsin.« less

Contributions of the three CYP1 monooxygenases to pro-inflammatory and inflammation-resolution lipid mediator pathways.

PubMed

Divanovic, Senad; Dalli, Jesmond; Jorge-Nebert, Lucia F; Flick, Leah M; Gálvez-Peralta, Marina; Boespflug, Nicholas D; Stankiewicz, Traci E; Fitzgerald, Jonathan M; Somarathna, Maheshika; Karp, Christopher L; Serhan, Charles N; Nebert, Daniel W

2013-09-15

All three cytochrome P450 1 (CYP1) monooxygenases are believed to participate in lipid mediator biosynthesis and/or their local inactivation; however, distinct metabolic steps are unknown. We used multiple-reaction monitoring and liquid chromatography-UV coupled with tandem mass spectrometry-based lipid-mediator metabololipidomics to identify and quantify three lipid-mediator metabolomes in basal peritoneal and zymosan-stimulated inflammatory exudates, comparing Cyp1a1/1a2/1b1(⁻/⁻) C57BL/6J-background triple-knockout mice with C57BL/6J wild-type mice. Significant differences between untreated triple-knockout and wild-type mice were not found for peritoneal cell number or type or for basal CYP1 activities involving 11 identified metabolic steps. Following zymosan-initiated inflammation, 18 lipid mediators were identified, including members of the eicosanoids and specialized proresolving mediators (i.e., resolvins and protectins). Compared with wild-type mice, Cyp1 triple-knockout mice exhibited increased neutrophil recruitment in zymosan-treated peritoneal exudates. Zymosan stimulation was associated with eight statistically significantly altered metabolic steps: increased arachidonic acid-derived leukotriene B₄ (LTB₄) and decreased 5S-hydroxyeicosatetraenoic acid; decreased docosahexaenoic acid-derived neuroprotectin D1/protectin D1, 17S-hydroxydocosahexaenoic acid, and 14S-hydroxydocosahexaenoic acid; and decreased eicosapentaenoic acid-derived 18R-hydroxyeicosapentaenoic acid (HEPE), 15S-HEPE, and 12S-HEPE. In neutrophils analyzed ex vivo, elevated LTB₄ levels were shown to parallel increased neutrophil numbers, and 20-hydroxy-LTB₄ formation was found to be deficient in Cyp1 triple-knockout mice. Together, these results demonstrate novel contributions of CYP1 enzymes to the local metabolite profile of lipid mediators that regulate neutrophilic inflammation.

Sequential Delivery of Cyclopeptide RA-V and Doxorubicin for Combination Therapy on Resistant Tumor and In Situ Monitoring of Cytochrome c Release

PubMed Central

Chen, Huachao; Wang, Yurong; Yao, Yongrong; Qiao, Shenglin; Wang, Hao; Tan, Ninghua

2017-01-01

A programmed drug delivery system that can achieve sequential release of multiple therapeutics under different stimulus holds great promise to enhance the treatment efficacy and overcome multi-drug resistance (MDR) in tumor. Herein, multi-organelle-targeted and pH/ cytochrome c (Cyt c) dual-responsive nanoparticles were designed for combination therapy on resistant tumor. In this system (designated DGLipo NPs), doxorubicin (Dox) was intercalated into the DNA duplex containing a Cyt c aptamer, which subsequently loaded in the dendrigraftpoly-L-lysines (DGL) cores of DGLipo NPs, while cyclopeptide RA-V was doped into the pH-sensitive liposomal shells. After dual modification with c(RGDfK) and mitochondria-penetrating peptide (MPP), DGLipo NPs could successively deliver the two drugs into lysosome and mitochondria of cancer cells, and achieve sequential drug release in virtue of the unique characteristic of these two organelles. The organelle-specific and spatiotemporally controlled release of Dox and RA-V led to enhanced therapeutic outcomes in MDR tumor. More significantly, the DGLipo NPs were successfully applied to monitor Cyt c release during mitochondria-mediated apoptotic process. This work represents a versatile strategy for precise combination therapy against resistant tumor with spatiotemporal control, and provides a potential tool for Cyt c-related apoptotic studies. PMID:29109776

Young adults, social networks, and addiction recovery: post treatment changes in social ties and their role as a mediator of 12-step participation.

PubMed

Kelly, John F; Stout, Robert L; Greene, M Claire; Slaymaker, Valerie

2014-01-01

Social factors play a key role in addiction recovery. Research with adults indicates individuals with substance use disorder (SUD) benefit from mutual-help organizations (MHOs), such as Alcoholics Anonymous, via their ability to facilitate adaptive network changes. Given the lower prevalence of sobriety-conducive, and sobriety-supportive, social contexts in the general population during the life-stage of young adulthood, however, 12-step MHOs may play an even more crucial recovery-supportive social role for young adults, but have not been investigated. Greater knowledge could enhance understanding of recovery-related change and inform young adults' continuing care recommendations. Emerging adults (N = 302; 18-24 yrs; 26% female; 95% White) enrolled in a study of residential treatment effectiveness were assessed at intake, 1, 3, 6, and 12 months on 12-step attendance, peer network variables ("high [relapse] risk" and "low [relapse] risk" friends), and treatment outcomes (Percent Days Abstinent; Percent Days Heavy Drinking). Hierarchical linear models tested for change in social risk over time and lagged mediational analyses tested whether 12-step attendance conferred recovery benefits via change in social risk. High-risk friends were common at treatment entry, but decreased during follow-up; low-risk friends increased. Contrary to predictions, while substantial recovery-supportive friend network changes were observed, this was unrelated to 12-step participation and, thus, not found to mediate its positive influence on outcome. Young adult 12-step participation confers recovery benefit; yet, while encouraging social network change, 12-step MHOs may be less able to provide social network change directly for young adults, perhaps because similar-aged peers are less common in MHOs. Findings highlight the importance of both social networks and 12-step MHOs and raise further questions as to how young adults benefit from 12-step MHOs.

Step-by-step guideline for disease-specific costing studies in low- and middle-income countries: a mixed methodology

PubMed Central

Hendriks, Marleen E.; Kundu, Piyali; Boers, Alexander C.; Bolarinwa, Oladimeji A.; te Pas, Mark J.; Akande, Tanimola M.; Agbede, Kayode; Gomez, Gabriella B.; Redekop, William K.; Schultsz, Constance; Tan, Siok Swan

2014-01-01

Background Disease-specific costing studies can be used as input into cost-effectiveness analyses and provide important information for efficient resource allocation. However, limited data availability and limited expertise constrain such studies in low- and middle-income countries (LMICs). Objective To describe a step-by-step guideline for conducting disease-specific costing studies in LMICs where data availability is limited and to illustrate how the guideline was applied in a costing study of cardiovascular disease prevention care in rural Nigeria. Design The step-by-step guideline provides practical recommendations on methods and data requirements for six sequential steps: 1) definition of the study perspective, 2) characterization of the unit of analysis, 3) identification of cost items, 4) measurement of cost items, 5) valuation of cost items, and 6) uncertainty analyses. Results We discuss the necessary tradeoffs between the accuracy of estimates and data availability constraints at each step and illustrate how a mixed methodology of accurate bottom-up micro-costing and more feasible approaches can be used to make optimal use of all available data. An illustrative example from Nigeria is provided. Conclusions An innovative, user-friendly guideline for disease-specific costing in LMICs is presented, using a mixed methodology to account for limited data availability. The illustrative example showed that the step-by-step guideline can be used by healthcare professionals in LMICs to conduct feasible and accurate disease-specific cost analyses. PMID:24685170

BCR®-701: a review of 10-years of sequential extraction analyses.

PubMed

Sutherland, Ross A

2010-11-08

A detailed quantitative analysis was performed on data presented in the literature that focused on the sequential extraction of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) from the certified reference material BCR-701 (lake sediment) using the three-step harmonized BCR(®) procedure. The accuracy of data reported in the literature, including precision and different measures of trueness, was assessed relative to the certified values for BCR-701. Forty data sets were accepted following extreme outlier removal, and statistically summarized with measures of central tendency, dispersion, and distribution form. In general, literature data were similar in their measurement precision to the expert laboratories used to certify the trace element contents in BCR-701. The overall median precision for literature reported data was 10% (range 6-19%), compared to certifying laboratories of 9% (range 4-33%). One measure of literature data trueness was assessed via a confirmatory approach using a robust bootstrap method. Only 22% of the comparisons indicated significantly different (all were lower) concentrations reported in the literature compared to certified values. The question of whether the differences are practically significant for environmental studies is raised. Bias was computed as a measure of trueness, and literature data were more frequently negatively biased, indicating lower concentrations reported in the literature for the six trace elements for the three-step sequential procedure compared to the certified values. However, 95% confidence intervals about the average bias for the 18 comparisons indicated only four instances when a mean bias of 0 (i.e., measured=certified) was not incorporated-suggesting statistical difference. Finally, Z-scores incorporating a Horwitz-type function were used to assess the general trueness of laboratory data. Of the 468 laboratory Z-score values computed, 92% were considered to be satisfactory, 5% were questionable, and 3% were unsatisfactory. A detailed examination of the methodology sections of the various studies showed that despite claiming adherence to the harmonized BCR sequential extraction protocol, significant deviations were commonly observed; particularly in moisture correction, sample mass, centrifugation specifics, shaking specifics, and incorporation of filtration. It is likely that failure to strictly adhere to the protocol adversely impacted accuracy, by increasing the degree of imprecision and resulting in more discrepant trueness values. Copyright © 2010 Elsevier B.V. All rights reserved.

What Learning Looks Like: Mediated Learning in Theory and Practice, K-6

ERIC Educational Resources Information Center

Feuerstein, Reuven; Lewin-Benham, Ann

2012-01-01

In this unique collaboration, the authors bring to life the theory of mediated learning. Through numerous examples and scenarios from classrooms and museums, they show how mediated learning helps children to become more effective learners. Readers learn the steps in the process, including analyzing the child's problem, teaching the child to focus…

Regulation of corneal stroma extracellular matrix assembly.

PubMed

Chen, Shoujun; Mienaltowski, Michael J; Birk, David E

2015-04-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predicting orogenic wedge styles as a function of analogue erosion law and material softening

NASA Astrophysics Data System (ADS)

Mary, Baptiste C. L.; Maillot, Bertrand; Leroy, Yves M.

2013-10-01

The evolution of a compressive frictional wedge on a weak, frictional and planar décollement, subjected to frontal accretion, is predicted with a two step method called sequential limit analysis. The first step consists in finding, with the kinematic approach of limit analysis, the length of the active décollement and the dips of the emerging ramp and of the conjugate shear plane composing the emerging thrust fold. The second step leads to a modification of the geometry, first, because of the thrust fold development due to compression and, second, because of erosion. Erosion consists in removing periodically any material above a fictitious line at a selected slope, as done in analogue experiments. This application of sequential limit analysis generalizes the critical Coulomb wedge theory since it follows the internal deformation development. With constant frictional properties, the deformation is mostly diffuse, a succession of thrust folds being activated so that the topographic slope reaches exactly the theoretical, critical value. Frictional weakening on the ramps results in a deformation style composed of thrust sheets and horses. Applying an erosion slope at the critical topographic value leads to exhumation in the frontal, central, or rear region of the wedge depending on the erosion period and the weakening. Erosion at slopes slightly above or below the critical value results in exhumation toward the foreland or the hinterland, respectively, regardless of the erosion period. Exhumation is associated with duplexes, imbricate fans, antiformal stacks, and major backthrusting. Comparisons with sandbox experiments confirm that the thickness, dips, vergence, and exhumation of thrust sheets can be reproduced with friction and erosion parameters within realistic ranges of values.

STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance

PubMed Central

Kim, Yoon-Jung; Kang, Young; Park, Hye-Yeon; Lee, Jae-Ran; Yu, Dae-Yeul; Murata, Takuya; Gondo, Yoichi; Hwang, Jung Hwan; Kim, Yong-Hoon; Lee, Chul-Ho; Rhee, Myungchull; Han, Pyung-Lim; Chung, Bong-Hyun; Lee, Hyun-Jun; Kim, Kyoung-Shim

2016-01-01

Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEPC230X−/− mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEPC230X−/− mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine. PMID:26915673

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

PubMed

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-10-30

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

[Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

PubMed

Allouche, G

2016-02-01

Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses and recurrences, in antidepressant maintenance. These data support the interest of therapeutic strategies based on evolutionary criteria. Sequential models inspired by statistical methods may incorporate the effects of a future treatment by measuring the current one. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Pattern formation and geometry of the manifold

NASA Astrophysics Data System (ADS)

Haji, Amir Hossein; Mahzoon, Mojtaba; Javadpour, Sirus

2011-03-01

The objective of the present work is to investigate how pattern formation in the Cahn-Hilliard system can be influenced by geometry of the manifold. This is in contrast to control methods in which the physical field is modified and the pattern formation of the original system changes in response to control inputs. The idea begins with the cylindrical manifold symmetry leading to circumferential rolls while the torus manifold can be used to produce and control helical rolls. The next step is to search for a weaker restriction on the geometry of the manifold in order to reduce its dimension. In particular a short amplitude sinusoidal modulation on a flat surface is studied. At the final step a sequential pattern formation is presented.

Step wise, multiple objective calibration of a hydrologic model for a snowmelt dominated basin

USGS Publications Warehouse

Hay, L.E.; Leavesley, G.H.; Clark, M.P.; Markstrom, S.L.; Viger, R.J.; Umemoto, M.

2006-01-01

The ability to apply a hydrologic model to large numbers of basins for forecasting purposes requires a quick and effective calibration strategy. This paper presents a step wise, multiple objective, automated procedure for hydrologic model calibration. This procedure includes the sequential calibration of a model's simulation of solar radiation (SR), potential evapotranspiration (PET), water balance, and daily runoff. The procedure uses the Shuffled Complex Evolution global search algorithm to calibrate the U.S. Geological Survey's Precipitation Runoff Modeling System in the Yampa River basin of Colorado. This process assures that intermediate states of the model (SR and PET on a monthly mean basis), as well as the water balance and components of the daily hydrograph are simulated, consistently with measured values.

Gas Separation Using Organic-Vapor-Resistent Membranes In Conjunctin With Organic-Vapor-Selective Membranes

DOEpatents

Baker, Richard W.; Pinnau, Ingo; He, Zhenjie; Da Costa, Andre R.; Daniels, Ramin; Amo, Karl D.; Wijmans, Johannes G.

2003-06-03

A process for treating a gas mixture containing at least an organic compound gas or vapor and a second gas, such as natural gas, refinery off-gas or air. The process uses two sequential membrane separation steps, one using membrane selective for the organic compound over the second gas, the other selective for the second gas over the organic vapor. The second-gas-selective membranes use a selective layer made from a polymer having repeating units of a fluorinated polymer, and demonstrate good resistance to plasticization by the organic components in the gas mixture under treatment, and good recovery after exposure to liquid aromatic hydrocarbons. The membrane steps can be combined in either order.

Modeling snail breeding in a bioregenerative life support system

NASA Astrophysics Data System (ADS)

Kovalev, V. S.; Manukovsky, N. S.; Tikhomirov, A. A.; Kolmakova, A. A.

2015-07-01

The discrete-time model of snail breeding consists of two sequentially linked submodels: "Stoichiometry" and "Population". In both submodels, a snail population is split up into twelve age groups within one year of age. The first submodel is used to simulate the metabolism of a single snail in each age group via the stoichiometric equation; the second submodel is used to optimize the age structure and the size of the snail population. Daily intake of snail meat by crewmen is a guideline which specifies the population productivity. The mass exchange of the snail unit inhabited by land snails of Achatina fulica is given as an outcome of step-by-step modeling. All simulations are performed using Solver Add-In of Excel 2007.

Crop status evaluations and yield predictions

NASA Technical Reports Server (NTRS)

Haun, J. R.

1975-01-01

A model was developed for predicting the day 50 percent of the wheat crop is planted in North Dakota. This model incorporates location as an independent variable. The Julian date when 50 percent of the crop was planted for the nine divisions of North Dakota for seven years was regressed on the 49 variables through the step-down multiple regression procedure. This procedure begins with all of the independent variables and sequentially removes variables that are below a predetermined level of significance after each step. The prediction equation was tested on daily data. The accuracy of the model is considered satisfactory for finding the historic dates on which to initiate yield prediction model. Growth prediction models were also developed for spring wheat.

Statistical models for detecting differential chromatin interactions mediated by a protein.

PubMed

Niu, Liang; Li, Guoliang; Lin, Shili

2014-01-01

Chromatin interactions mediated by a protein of interest are of great scientific interest. Recent studies show that protein-mediated chromatin interactions can have different intensities in different types of cells or in different developmental stages of a cell. Such differences can be associated with a disease or with the development of a cell. Thus, it is of great importance to detect protein-mediated chromatin interactions with different intensities in different cells. A recent molecular technique, Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET), which uses formaldehyde cross-linking and paired-end sequencing, is able to detect genome-wide chromatin interactions mediated by a protein of interest. Here we proposed two models (One-Step Model and Two-Step Model) for two sample ChIA-PET count data (one biological replicate in each sample) to identify differential chromatin interactions mediated by a protein of interest. Both models incorporate the data dependency and the extent to which a fragment pair is related to a pair of DNA loci of interest to make accurate identifications. The One-Step Model makes use of the data more efficiently but is more computationally intensive. An extensive simulation study showed that the models can detect those differentially interacted chromatins and there is a good agreement between each classification result and the truth. Application of the method to a two-sample ChIA-PET data set illustrates its utility. The two models are implemented as an R package MDM (available at http://www.stat.osu.edu/~statgen/SOFTWARE/MDM).

Statistical Models for Detecting Differential Chromatin Interactions Mediated by a Protein

PubMed Central

Niu, Liang; Li, Guoliang; Lin, Shili

2014-01-01

Chromatin interactions mediated by a protein of interest are of great scientific interest. Recent studies show that protein-mediated chromatin interactions can have different intensities in different types of cells or in different developmental stages of a cell. Such differences can be associated with a disease or with the development of a cell. Thus, it is of great importance to detect protein-mediated chromatin interactions with different intensities in different cells. A recent molecular technique, Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET), which uses formaldehyde cross-linking and paired-end sequencing, is able to detect genome-wide chromatin interactions mediated by a protein of interest. Here we proposed two models (One-Step Model and Two-Step Model) for two sample ChIA-PET count data (one biological replicate in each sample) to identify differential chromatin interactions mediated by a protein of interest. Both models incorporate the data dependency and the extent to which a fragment pair is related to a pair of DNA loci of interest to make accurate identifications. The One-Step Model makes use of the data more efficiently but is more computationally intensive. An extensive simulation study showed that the models can detect those differentially interacted chromatins and there is a good agreement between each classification result and the truth. Application of the method to a two-sample ChIA-PET data set illustrates its utility. The two models are implemented as an R package MDM (available at http://www.stat.osu.edu/~statgen/SOFTWARE/MDM). PMID:24835279

Disentangling beat perception from sequential learning and examining the influence of attention and musical abilities on ERP responses to rhythm.

PubMed

Bouwer, Fleur L; Werner, Carola M; Knetemann, Myrthe; Honing, Henkjan

2016-05-01

Beat perception is the ability to perceive temporal regularity in musical rhythm. When a beat is perceived, predictions about upcoming events can be generated. These predictions can influence processing of subsequent rhythmic events. However, statistical learning of the order of sounds in a sequence can also affect processing of rhythmic events and must be differentiated from beat perception. In the current study, using EEG, we examined the effects of attention and musical abilities on beat perception. To ensure we measured beat perception and not absolute perception of temporal intervals, we used alternating loud and soft tones to create a rhythm with two hierarchical metrical levels. To control for sequential learning of the order of the different sounds, we used temporally regular (isochronous) and jittered rhythmic sequences. The order of sounds was identical in both conditions, but only the regular condition allowed for the perception of a beat. Unexpected intensity decrements were introduced on the beat and offbeat. In the regular condition, both beat perception and sequential learning were expected to enhance detection of these deviants on the beat. In the jittered condition, only sequential learning was expected to affect processing of the deviants. ERP responses to deviants were larger on the beat than offbeat in both conditions. Importantly, this difference was larger in the regular condition than in the jittered condition, suggesting that beat perception influenced responses to rhythmic events in addition to sequential learning. The influence of beat perception was present both with and without attention directed at the rhythm. Moreover, beat perception as measured with ERPs correlated with musical abilities, but only when attention was directed at the stimuli. Our study shows that beat perception is possible when attention is not directed at a rhythm. In addition, our results suggest that attention may mediate the influence of musical abilities on beat perception. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Computational time reduction for sequential batch solutions in GNSS precise point positioning technique

NASA Astrophysics Data System (ADS)

Martín Furones, Angel; Anquela Julián, Ana Belén; Dimas-Pages, Alejandro; Cos-Gayón, Fernando

2017-08-01

Precise point positioning (PPP) is a well established Global Navigation Satellite System (GNSS) technique that only requires information from the receiver (or rover) to obtain high-precision position coordinates. This is a very interesting and promising technique because eliminates the need for a reference station near the rover receiver or a network of reference stations, thus reducing the cost of a GNSS survey. From a computational perspective, there are two ways to solve the system of observation equations produced by static PPP either in a single step (so-called batch adjustment) or with a sequential adjustment/filter. The results of each should be the same if they are both well implemented. However, if a sequential solution (that is, not only the final coordinates, but also those observed in previous GNSS epochs), is needed, as for convergence studies, finding a batch solution becomes a very time consuming task owing to the need for matrix inversion that accumulates with each consecutive epoch. This is not a problem for the filter solution, which uses information computed in the previous epoch for the solution of the current epoch. Thus filter implementations need extra considerations of user dynamics and parameter state variations between observation epochs with appropriate stochastic update parameter variances from epoch to epoch. These filtering considerations are not needed in batch adjustment, which makes it attractive. The main objective of this research is to significantly reduce the computation time required to obtain sequential results using batch adjustment. The new method we implemented in the adjustment process led to a mean reduction in computational time by 45%.

Sequential chemical treatment of radium species in TENORM waste sludge produced from oil and natural gas production.

PubMed

El Afifi, E M; Awwad, N S; Hilal, M A

2009-01-30

This paper is dedicated to the treatment of sludge occurring in frame of the Egyptian produced from oil and gas production. The activity levels of three radium isotopes: Ra-226 (of U-series), Ra-228 and Ra-224 (of Th-series) in the solid TENORM waste (sludge) were first evaluated and followed by a sequential treatment for all radium species (fractions) presented in TENORM. The sequential treatment was carried out based on two approaches 'A' and 'B' using different chemical solutions. The results obtained indicate that the activity levels of all radium isotopes (Ra-226, Ra-228 and Ra-224) of the environmental interest in the TENORM waste sludge were elevated with regard to exemption levels established by IAEA [International Atomic Energy Agency (IAEA), International basic safety standards for the protection against ionizing radiation and for the safety of radiation sources. GOV/2715/Vienna, 1994]. Each approach of the sequential treatment was performed through four steps using different chemical solutions to reduce the activity concentration of radium in a large extent. Most of the leached radium was found as an oxidizable Ra species. The actual removal % leached using approach B was relatively efficient compared to A. It is observed that the actual removal percentages (%) of Ra-226, Ra-228 and Ra-224 using approach A are 78+/-2.8, 64.8+/-4.1 and 76.4+/-5.2%, respectively. Whereas in approach A, the overall removal % of Ra-226, Ra-228 and Ra-228 was increased to approximately 91+/-3.5, 87+/-4.1 and 90+/-6.2%, respectively.

Comparative study of six sequential spectrophotometric methods for quantification and separation of ribavirin, sofosbuvir and daclatasvir: An application on Laboratory prepared mixture, pharmaceutical preparations, spiked human urine, spiked human plasma, and dissolution test.

PubMed

Hassan, Wafaa S; Elmasry, Manal S; Elsayed, Heba M; Zidan, Dalia W

2018-09-05

In accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, six novel, simple and precise sequential spectrophotometric methods were developed and validated for the simultaneous analysis of Ribavirin (RIB), Sofosbuvir (SOF), and Daclatasvir (DAC) in their mixture without prior separation steps. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. These techniques consisted of several sequential steps using zero, ratio and/or derivative spectra. DAC was first determined through direct spectrophotometry at 313.7 nm without any interference of the other two drugs while RIB and SOF can be determined after ratio subtraction through five methods; Ratio difference spectrophotometric method, successive derivative ratio method, constant center, isoabsorptive method at 238.8 nm, and mean centering of the ratio spectra (MCR) at 224 nm and 258 nm for RIB and SOF, respectively. The calibration curve is linear over the concentration ranges of (6-42), (10-70) and (4-16) μg/mL for RIB, SOF, and DAC, respectively. This method was successfully applied to commercial pharmaceutical preparation of the drugs, spiked human urine, and spiked human plasma. The above methods are very simple methods that were developed for the simultaneous determination of binary and ternary mixtures and so enhance signal-to-noise ratio. The method has been successfully applied to the simultaneous analysis of RIB, SOF, and DAC in laboratory prepared mixtures. The obtained results are statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05. Copyright © 2018 Elsevier B.V. All rights reserved.

Building emotional resilience over 14 sessions of emotion focused therapy: Micro-longitudinal analyses of productive emotional patterns.

PubMed

Pascual-Leone, A; Yeryomenko, N; Sawashima, T; Warwar, S

2017-05-04

Pascual-Leone and Greenberg's sequential model of emotional processing has been used to explore process in over 24 studies. This line of research shows emotional processing in good psychotherapy often follows a sequential order, supporting a saw-toothed pattern of change within individual sessions (progressing "2-steps-forward, 1-step-back"). However, one cannot assume that local in-session patterns are scalable across an entire course of therapy. Thus, the primary objective of this exploratory study was to consider how the sequential patterns identified by Pascual-Leone, may apply across entire courses of treatment. Intensive emotion coding in two separate single-case designs were submitted for quantitative analyses of longitudinal patterns. Comprehensive coding in these cases involved recording observations for every emotional event in an entire course of treatment (using the Classification of Affective-Meaning States), which were then treated as a 9-point ordinal scale. Applying multilevel modeling to each of the two cases showed significant patterns of change over a large number of sessions, and those patterns were either nested at the within-session level or observed at the broader session-by-session level of change. Examining successful treatment cases showed several theoretically coherent kinds of temporal patterns, although not always in the same case. Clinical or methodological significance of this article: This is the first paper to demonstrate systematic temporal patterns of emotion over the course of an entire treatment. (1) The study offers a proof of concept that longitudinal patterns in the micro-processes of emotion can be objectively derived and quantified. (2) It also shows that patterns in emotion may be identified on the within-session level, as well as the session-by-session level of analysis. (3) Finally, observed processes over time support the ordered pattern of emotional states hypothesized in Pascual-Leone and Greenberg's ( 2007 ) model of emotional processing.

The effect of illumination on the formation of metal halide perovskite films

NASA Astrophysics Data System (ADS)

Ummadisingu, Amita; Steier, Ludmilla; Seo, Ji-Youn; Matsui, Taisuke; Abate, Antonio; Tress, Wolfgang; Grätzel, Michael

2017-04-01

Optimizing the morphology of metal halide perovskite films is an important way to improve the performance of solar cells when these materials are used as light harvesters, because film homogeneity is correlated with photovoltaic performance. Many device architectures and processing techniques have been explored with the aim of achieving high-performance devices, including single-step deposition, sequential deposition and anti-solvent methods. Earlier studies have looked at the influence of reaction conditions on film quality, such as the concentration of the reactants and the reaction temperature. However, the precise mechanism of the reaction and the main factors that govern it are poorly understood. The consequent lack of control is the main reason for the large variability observed in perovskite morphology and the related solar-cell performance. Here we show that light has a strong influence on the rate of perovskite formation and on film morphology in both of the main deposition methods currently used: sequential deposition and the anti-solvent method. We study the reaction of a metal halide (lead iodide) with an organic compound (methylammonium iodide) using confocal laser scanning fluorescence microscopy and scanning electron microscopy. The lead iodide crystallizes before the intercalation of methylammonium iodide commences, producing the methylammonium lead iodide perovskite. We find that the formation of perovskite via such a sequential deposition is much accelerated by light. The influence of light on morphology is reflected in a doubling of solar-cell efficiency. Conversely, using the anti-solvent method to form methyl ammonium lead iodide perovskite in a single step from the same starting materials, we find that the best photovoltaic performance is obtained when films are produced in the dark. The discovery of light-activated crystallization not only identifies a previously unknown source of variability in opto-electronic properties, but also opens up new ways of tuning morphology and structuring perovskites for various applications.

The exoribonuclease Nibbler controls 3' end processing of microRNAs in Drosophila.

PubMed

Liu, Nan; Abe, Masashi; Sabin, Leah R; Hendriks, Gert-Jan; Naqvi, Ammar S; Yu, Zhenming; Cherry, Sara; Bonini, Nancy M

2011-11-22

MicroRNAs (miRNAs) are endogenous noncoding small RNAs with important roles in many biological pathways; their generation and activity are under precise regulation [1-3]. Emerging evidence suggests that miRNA pathways are precisely modulated with controls at the level of transcription [4-8], processing [9-11], and stability [12, 13], with miRNA deregulation linked with diseases [14] and neurodegenerative disorders [15]. In the Drosophila miRNA biogenesis pathway, long primary miRNA transcripts undergo sequential cleavage [16-18] to release the embedded miRNAs. Mature miRNAs are then loaded into Argonaute1 (Ago1) within the RNA-induced silencing complex (RISC) [19, 20]. Intriguingly, we found that Drosophila miR-34 displays multiple isoforms that differ at the 3' end, suggesting a novel biogenesis mechanism involving 3' end processing. To define the cellular factors responsible, we performed an RNA interference (RNAi) screen and identified a putative 3'→5' exoribonuclease CG9247/nibbler essential for the generation of the smaller isoforms of miR-34. Nibbler (Nbr) interacts with Ago1 and processes miR-34 within RISC. Deep sequencing analysis revealed a larger set of multi-isoform miRNAs that are controlled by nibbler. These findings suggest that Nbr-mediated 3' end processing represents a critical step in miRNA maturation that impacts miRNA diversity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Exosites in the substrate specificity of blood coagulation reactions.

PubMed

Bock, P E; Panizzi, P; Verhamme, I M A

2007-07-01

The specificity of blood coagulation proteinases for substrate, inhibitor, and effector recognition is mediated by exosites on the surfaces of the catalytic domains, physically separated from the catalytic site. Some thrombin ligands bind specifically to either exosite I or II, while others engage both exosites. The involvement of different, overlapping constellations of exosite residues enables binding of structurally diverse ligands. The flexibility of the thrombin structure is central to the mechanism of complex formation and the specificity of exosite interactions. Encounter complex formation is driven by electrostatic ligand-exosite interactions, followed by conformational rearrangement to a stable complex. Exosites on some zymogens are in low affinity proexosite states and are expressed concomitant with catalytic site activation. The requirement for exosite expression controls the specificity of assembly of catalytic complexes on the coagulation pathway, such as the membrane-bound factor Xa*factor Va (prothrombinase) complex, and prevents premature assembly. Substrate recognition by prothrombinase involves a two-step mechanism with initial docking of prothrombin to exosites, followed by a conformational change to engage the FXa catalytic site. Prothrombin and its activation intermediates bind prothrombinase in two alternative conformations determined by the zymogen to proteinase transition that are hypothesized to involve prothrombin (pro)exosite I interactions with FVa, which underpin the sequential activation pathway. The role of exosites as the major source of substrate specificity has stimulated development of exosite-targeted anticoagulants for treatment of thrombosis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yanwu; Wang, Xiaoxia; Hawkins, Cheryl A.

The LIM-only adaptor PINCH (the particularly interesting cysteine- and histidine-rich protein) plays a pivotal role in the assembly of focal adhesions (FAs), supramolecular complexes that transmit mechanical and biochemical information between extracellular matrix and actin cytoskeleton, regulating diverse cell adhesive processes such as cell migration, cell spreading, and survival. A key step for the PINCH function is its localization to FAs, which depends critically on the tight binding of PINCH to integrin-linked kinase (ILK). Here we report the solution NMR structure of the core ILK {center_dot} PINCH complex (28 kDa, K{sub D} {approx} 68 nm) involving the N-terminal ankyrin repeatmore » domain (ARD) of ILK and the first LIM domain (LIM1) of PINCH. We show that the ILK ARD exhibits five sequentially stacked ankyrin repeat units, which provide a large concave surface to grip the two contiguous zinc fingers of the PINCH LIM1. The highly electrostatic interface is evolutionally conserved but differs drastically from those of known ARD and LIM bound to other types of protein domains. Consistently mutation of a hot spot in LIM1, which is not conserved in other LIM domains, disrupted the PINCH binding to ILK and abolished the PINCH targeting to FAs. These data provide atomic insight into a novel modular recognition and demonstrate how PINCH is specifically recruited by ILK to mediate the FA assembly and cell-extracellular matrix communication.« less

Basketball lay-up - foot loading characteristics and the number of trials necessary to obtain stable plantar pressure variables.

PubMed

Chua, YaoHui K; Quek, Raymond K K; Kong, Pui W

2017-03-01

This study aimed (1) to profile the plantar loading characteristics when performing the basketball lay-up in a realistic setting and (2) to determine the number of trials necessary to establish a stable mean for plantar loading variables during the lay-up. Thirteen university male basketball players [age: 23.0 (1.4) years, height: 1.75 (0.05) m, mass: 68.4 (8.6) kg] performed ten successful basketball lay-ups from a stationary position. Plantar loading variables were recorded using the Novel Pedar-X in-shoe system. Loading variables including peak force, peak pressure, and pressure-time integral were extracted from eight foot regions. Performance stability of plantar loading variables during the take-off and landing steps were assessed using the sequential averaging technique and intra-class correlation coefficient (ICC). High plantar loadings were experienced at the heel during the take-off steps, and both the heel and forefoot regions upon landing. The sequential estimation technique revealed a five-eight trial range to achieve a stable mean across all plantar loading variables, whereas ICC analysis was insensitive to inter-trial differences of repeated lay-up performances. Future studies and performance evaluation protocols on plantar loading during basketball lay-ups should include at least eight trials to ensure that the measurements obtained are sufficiently stable.

Sequential estimation of surface water mass changes from daily satellite gravimetry data

NASA Astrophysics Data System (ADS)

Ramillien, G. L.; Frappart, F.; Gratton, S.; Vasseur, X.

2015-03-01

We propose a recursive Kalman filtering approach to map regional spatio-temporal variations of terrestrial water mass over large continental areas, such as South America. Instead of correcting hydrology model outputs by the GRACE observations using a Kalman filter estimation strategy, regional 2-by-2 degree water mass solutions are constructed by integration of daily potential differences deduced from GRACE K-band range rate (KBRR) measurements. Recovery of regional water mass anomaly averages obtained by accumulation of information of daily noise-free simulated GRACE data shows that convergence is relatively fast and yields accurate solutions. In the case of cumulating real GRACE KBRR data contaminated by observational noise, the sequential method of step-by-step integration provides estimates of water mass variation for the period 2004-2011 by considering a set of suitable a priori error uncertainty parameters to stabilize the inversion. Spatial and temporal averages of the Kalman filter solutions over river basin surfaces are consistent with the ones computed using global monthly/10-day GRACE solutions from official providers CSR, GFZ and JPL. They are also highly correlated to in situ records of river discharges (70-95 %), especially for the Obidos station where the total outflow of the Amazon River is measured. The sparse daily coverage of the GRACE satellite tracks limits the time resolution of the regional Kalman filter solutions, and thus the detection of short-term hydrological events.

Full coverage of perovskite layer onto ZnO nanorods via a modified sequential two-step deposition method for efficiency enhancement in perovskite solar cells

NASA Astrophysics Data System (ADS)

Ruankham, Pipat; Wongratanaphisan, Duangmanee; Gardchareon, Atcharawon; Phadungdhitidhada, Surachet; Choopun, Supab; Sagawa, Takashi

2017-07-01

Full coverage of perovskite layer onto ZnO nanorod substrates with less pinholes is crucial for achieving high-efficiency perovskite solar cells. In this work, a two-step sequential deposition method is modified to achieve an appropriate property of perovskite (MAPbI3) film. Surface treatment of perovskite layer and its precursor have been systematically performed and their morphologies have been investigated. By pre-wetting of lead iodide (PbI2) and letting it dry before reacting with methylammonium iodide (MAI) provide better coverage of perovskite film onto ZnO nanorod substrate than one without any treatment. An additional MAI deposition followed with toluene drop-casting technique on the perovskite film is also found to increase the coverage and enhance the transformation of PbI2 to MAPbI3. These lead to longer charge carrier lifetime, resulting in an enhanced power conversion efficiency (PCE) from 1.21% to 3.05%. The modified method could been applied to a complex ZnO nanorods/TiO2 nanoparticles substrate. The enhancement in PCE to 3.41% is observed. These imply that our introduced method provides a simple way to obtain the full coverage and better transformation to MAPbI3 phase for enhancement in performances of perovskite solar cells.